Ethical Examination of the Mortgage Meltdown

Ethical Examination of the Mortgage Meltdown The subprime mortgage crisis, commonly referred to as the mortgage meltdown, unveiled itself after a sharp increase in home foreclosures beginning in 2006, which unfolded seemingly out of control by 2007. American spending declined, the housing market plunged, foreclosures continued to climb and the stock market was shaken. The subprime crisis and resulting foreclosures prompted discord among consumers, lenders and legislators all bound to one another by a web of complex financial engineering. The event represents a turning point in the world economy and our culture as fundamental societal changes are needed to rebuild the relationship between the U.S. government, Wall Street institutions, and the average American. Unethical decisions from various parties have altered the way future business will be conducted as the current economic and political policies were unable to confront the crisis before it unraveled. This paper is focused on investigating the unfavorable effects of the curr ent financial system structure established on unbreakable bonds of linkage among American communities and financial institutions. Initially, many financial experts including the International Monetary Fund (IMF) believed the crisis would be limited within the arena of mortgage lenders who had accumulated these subprime loans. But as time progressed there was an evident spread into the prime commercial and residential real estate markets as well as an impact on consumer credit. In an April 2008 Global Financial Stability Report, the IMF criticized the excessive risk-taking and weak underwriting undertaken by under-capitalized institutions and recommended measures including ratings systems reform and a change in compensation schemes for managers of financial institutions (Smith, 2009, p. 2). According to the IMF, there was a collective failure by financial institutions for not properly managing risk. The New York Times columnist Michiko Kakutani (2010) would add there were flawed mathematical models that most financial executives did not really understand themselves (Kakutani, p. 1). Essentially, Wall Street firm s turned subprime mortgages into exotic, toxic financial products by making a fortune laundering and reselling, and they were enabled in doing so by the very ratings agencies that were supposed to police risk (Kakutani, p.1). Even as the quality of the underlying loans appeared sketchy, few could have expected how the severity of the subprime fallout would threaten the U.S. economy to the degree it has so far. The idea behind subprime loans is borrowers who do not meet the credit requirements for prime mortgage loans are required to pay higher interest rates and fees than prime mortgage loans. Since a significant portion of new home ownership expansion stems from buyers with a lower income compared to historical norms, the initial down payment is relatively low. This creates more risk for lenders and requires higher interest rates attached to the monthly mortgage payment. The difference between the social and economic impact of historical home ownership compared to the subprime situation is the earlier loans created real ownership and wealth, which could be passed along to future generations. The illusion of wealth in subprime lending has led to instability within families and communities as many low-income borrowers were enticed by the ease of becoming a first-time homeowner (Muolo, 2008, p. 277-303). Its important to consider how subprime borrowers came from lower income families. Due to lower savings, they are unable to pay the typical 20% down payment on a house, thus requiring near 100% financing. This new form of lending allowed families who had previously been excluded from home-owning to participate in affordable housing programs. It was even referred to as creative financing. The common question at hand is identifying who is to blame for allowing the capital market economy to create irresponsible home ownership. Much of the subprime homes never yielded real wealth as outright ownership of the home was highly unlikely. Subprime lending to low-income people illustrates how leaders in power are able to raise awareness to followers that home ownership is a moral obligation. The leaders have demonstrated their ability to raise followers consciousness about what is and ought to be important to them (Ciulla, 2003, p. 220). The idea of home ownership even became a political agenda to make people feel like they deserve a new home. Comparisons could be made that our government was almost behaving as a Jim Jones leader. Jim Jones appealed generally to impoverished and minority individuals who felt oppressed and besieged by a hostile world. Similarly, the government allowed subprime lending to target individuals who were historically turned away. ETHICAL ANALYSIS OF MARKET CONDITIONS Understanding the ethical behaviors of the subprime fallout is rather challenging as many dynamics stem from the individual as well as from a societal level. First of all, a new research paper conducted by three respected Irish economists point to a common factor of irrational exuberance among the real estate bubbles experienced in America and Ireland. In both countries, buyers and lenders convinced themselves that real estate prices, although sky-high by historical standards, would continue to rise (Krugman, 2010, p. 2). Consequently, this prevalent belief cannot be explicitly linked to an individual as society collectively accepted these trends. Additionally, the common social viewpoint that rising incomes would continue to accommodate the rising price of homes is not any individuals responsibility. Perhaps, the forecasting models used by economic experts were excessively optimistic, but this does not make them morally irresponsible. Robert Shiller (2008) argues the housing bubble that created the subprime crisis ultimately grew as big as it did because we as a society do not understand, or know how to deal with, speculative bubbles (p. 3). It is difficult to affix an ethical verdict to something as uncontained as the market. However, a slice of moral accountability should be ascribed to key leaders who have control in shaping the market. There was a form of regulatory imprudence as the people charged with keeping banks safe didnt do their job (Krugman, 2010, p. 2). While many regulators looked the other way, the bigger issue is the ideology based on free-market fundamentalism where deregulation was thought to strengthen the financial system. The Federal Reserve chairman, Alan Greenspan, was criticized for maintaining low interest rates that further provoked subprime lending. Due to many stakeholders in the subprime story, blame has been placed on many factors such as a growing dishonesty among mortgage lenders, increasing greed among securitizers, hedge funds, and rating agencies (Shiller, 2008, p. 4). But, we can identify that Greenspan had direct control over key monetary policies such as interest rates, with foreseeable impacts. Justifying whether poor judgment was made in these decisions illustrates a moral question of his accountability. Many others question how well the government addressed regulation policies and the freedom given to banking institutions to issue reckless lending. It is also logical to believe the government essentially allowed an over inflation of homes in the market. Their openhanded efforts in rescuing weakening financial institutions beginning in 2008 with Bear Stearns, then AIG, and many others may indicate a form of duty the government has to help make amends for allowing too many Americans to have a mortgage they are unable to afford. The American financial system is filled with firms that disdain the need for government regulation in good times but insist on being rescued by the government in bad times (Kakutani, 2010, p. 2). Nevertheless, prescribing all of the liability upon the government or Federal Reserve is too unbalanced. The complex nature of the economic conditions related to the subprime crisis is larger than what any single stakeholder could instigate. Helping to fuel new mortgages, brokers sought to attract home-buyers with no money down agreements. Some likely acted of the premises that housing values and real incomes would gradually keep climbing to create a win-win situation for both parties. Again, to assign a moral indiscretion to a specific mortgage broker supplied with the best available public information to guide potential buyers is unsupported. It is not appropriate to directly attribute their actions to the subprime meltdown. But, as we continue to analyze behaviors we will see how many individuals took advantage of the economic zeal that fueled the subprime crisis (Cohan, 2009, p. 92-108). Much of what has been discussed points to the common belief of increasing prosperity and as well as a general unsupported belief in maintaining such high growth. There is quite a fine line between having sustained optimism for a bright future and a greed-like attitude that tries to hide the reality of an eventual economic decline. Would it be acceptable to morally blame society as a whole for overlooking the apparent signs of danger? Not fully. Yet, as more players in the market are outlined in the following sections we will see how the rules of the game may have deliberately hurt others. ETHICAL ANALYSIS OF KEY PLAYERS To expand upon the market condition section previously discussed the moral responsibility in the transactional loan process is analyzed next. There is a duty for each party to have transparency and truthfulness when completing a deal. Ideally, the consumer is obligated to pay loans they agree upon with the broker. As government leaders portray the promise for all Americans to have prosperity, home ownership became a reality for the most economically impoverished people. We begin to see a fabrication of falsely portrayed subprime loan applications by consumers captivated by these lucrative opportunities to have a new house. It would seem morally wrong for a person to falsify information, as most people should only want to acquire a loan they can manage with financial responsibility. However, the self-interest of satisfying their desire overcame the normal way of managing finances. There also presents a moral hazard to the broker who works for commission by getting people to sign agree ments and has no financial liability afterwards. Is the broker seeking the best interests in protecting customers? We realize the lack of concern by many brokers who overlooked the details. Ironically, as many of the brokers did not fully consider the unethical transactions, they are now the ones out of a job (Andrews, 2009, p. 133-148.). Furthermore, the lenders or banks are presented with ethical considerations as to how well they scanned applicants before providing loans. Were loan requirements not strict enough on purpose? It would seem a bad business practice to grant loans knowing customers will have late or no payments towards the principal of the loan. As we have learned, the banks ended up selling the bad loans to investors. The analysis up to this point seems to be pointing toward the idea that owning a home is becoming a morally acceptable idea and a basic right for everyone. Envision subprime loans as being a prescription drug. When placed in the hands of a diagnosed person in need of the drug, it can bring about social good, but if given to a teenager, who has no need for it, the drug can lead to destruction. This illustration shows how subprime loans require proper structuring to provide the most good. ETHICAL ANALYSIS OF FINANCIAL INSTITUTIONS AND INVESTORS Containing the misfortunate subprime loans solely between the lender and consumer could have benefited and alleviated the crisis if the loans were able to be paid by the new homeowner. But, due to lenders not making any profit on the loans they are forced to sell bad mortgages by packaging them in the form of collateralized debt in hopes of selling to investors who believe the value of the mortgage assets will increase. Again, we are confronted with the moral issue of how transparent these debt packages are represented. Do investors deserve better warning of the extreme risk of buying mortgage debts? Who is ultimately ethically accountable for selling bad debt? Everyone seemed to be caught up in this euphoria where no one expected anything bad to happen. To break down some of the moral culprits of passing along bad loans, many financial agencies were persuading clients to invest in bad debt, while at the same time these organizations sold off the loans to avoid any further losses. The apparent misuse seems morally wrong as they knowingly caused harm to investors. The rating agencies are also tossed into the blame game. Wall Street firms knew how to game the system; they knew how to get the rating agencies (which were eager to collect big fees for their services) to ineptly rate dangerous bonds (Kakutani, 2010, p. 2). Who is to protecting the financial stability of the economy by inaccurately rating risky subprime loans? Too many people assumed continued economic growth and overlooked the likelihood of the bubble bursting (Mason, 2009, p. 81-90). Overall, much of the calamity of the mortgage meltdown is due to the collective failure of society in a business and government sense to foresee the collapse, making it difficult to assign re sponsibility. PSYCHOLOGICAL IMPACTS The various examples presented have illustrated the psychology involved in the real estate bubble (Schiller, p. 4). From Paul Masons (2009) book we not only have witnessed capitalisms tendency to expand the power of the market to push for the maximum freedom (p. 171), but the tendency for a double movement as ascribed by the Hungarian philosopher Karl Polanyi. As free market expansion oftentimes reduces the relationships between families, nations, and social classes to a mere commercial level based on money, a counter-tendency arises to defend common human values and community. The dynamics of the economy will require a willingness of ordinary people to impose limits, standards and sustainability on capital (Mason, p. 172). The current form of our markets have possibilities for limitless growth, yet the often selfish and unequal society in which we live in has created repeated financial distress. PHILOSOPHICAL IMPLICATIONS As many people point to banks for significantly contributing to the economic downfall, understanding how philosophers approach the situation is important to further our awareness of the problem. The premise of Immanuel Kants categorical imperative is based on the morality of the act, not outcomes, meaning an act may be done for the right reasons, even if it has bad consequences (Ciulla, 2003, p. 95). So, how can a lending institute be judged as unethical for issuing loans to help customers purchase a home? The morality failure, based on this stance would not fall on the bank. But, consider Kants statement that all rational beings stand under the law that each of them should treat himself and all others never merely as a means but always at the same time as an end in himself (Ciulla, 2003, p. 107). If the bank fails to appropriately evaluate the clients ability to pay back debt, then they are treating the client as a means for their own financial benefit and are eventually leading the ir clients to an ethical failure. On the same token, the brokers who never bothered to properly perform background checks on their clients were also satisfying their own financial desires, rather than helping customers make sound financial choices. John Stuart Mills utilitarian approach emphasizes multiplying happiness, or making life better for the majority of stakeholders in an organization, a community, or a country (Ciulla, 2003, p. 143). Therefore, Mill would view the lending institutions as providing moral value to the individuals seeking to gain home ownership. The general economy and government polices were allowing and expanding housing programs, in which there was a collective agreement that having people buy homes was a good strategy for the country. We now realize the greatest good often looks different in the short term than in the long term. In retrospect, too much emphasis may have been placed on the present and not enough concern on potential consequences of too much lending. The multiplication of happiness for those involved in subprime lending only lasted until the foreclosures and collapse of the banking industry began. Just as Kant and Mills viewpoints speak of the moral behaviors among the parties involved, Ayn Rand offers insight by arguing that every man is an end in himself, he exists for his own sake, and the achievement of his own happiness is his highest moral purpose (Ciulla, 2003, p. 47). Her position seeks happiness proper to man and does not advise seeking happiness through fraudulent schemes as this approach will lead to frustration. She believes moralitys purpose isnt to command you to sacrifice your interests for the sake of others but rather to teach you the rational values and virtues happiness in fact requires. (Ghate, 2009, p. 3). In hopes of restoring society to the place we were before the collapse, Rand would not place the primary blame on the people, but the immoral system in which they had to act. There should be a reevaluation of what genuine self-interest consists of and whether the pursuit for happiness is moral. DEATH PLEDGE As mortgages have become a norm in the American society, there is an underlying meaning to the origin. The word mortgage comes from the Latin words, mort and gage. Mort means death, and gage means a pledge to forfeit something of value if a debt is not repaid. The basics of mortgages have remained the same; high value real estate which cannot be funded by most people results in borrowing money to buy property. Many people are enslaved to meet the death pledge they signed. Borrowers should be aware of what they are doing and realize it is not always justifiable to blame the banks, as they ultimately cannot force an individual to take on a mortgage obligation. (Marples, 2008, p. 2) There seems to be a moral dilemma confronting families who still owe more on their mortgages than what their home is worth. Should they sacrifice to pay their mortgage even though their homes value may not recover for several years? Or should they simply walk away (Merrel, 2009, p. 2)? If they made an agreement with a lender to pay the loan, then on the surface it would seem morally right to continue paying for the home. After understanding the significance of a death pledge, we could argue mortgages are not ethical documents, they are legal contracts (Merrel, 2009, p. 2). So, if a person decides to stop paying their mortgage, they simply pledge the ownership of the home back to the lender. Nevertheless, realize a mortgage contract entails a promise to pay and walking away from a promise in a way leads to a breach of ethics. It seems that determining whether it is morally justifiable in walking away has to be examined on a case to case basis. In respect to the people who lost their homes due to unemployment or other valid reasons, they have a right to be upset for how the careless decisions of others hurt their American Dream. It has turned into just that, a dream, as society allowed people to believe they deserve a home they cannot afford. John Rawls, a Harvard philosopher, offers insight to the economic and moral issues societies confront regarding distributive justice. He argues as self-interested rational beings governed by principles that oppose discrimination, everyone should have equal liberties and fair distribution. He speaks of inequalities among social class wealth as only being just if and only if they are part of a larger system on which they work out to the advantage of the most unfortunate representative man (Ciulla, 2003, p. 158). Why should we be making life better for those who are already well of with nice homes and do nothing for those who are already underprivileged? Perhaps, as in the case of subprim e lending, there was an outreach by leaders to provide equal opportunity to the least advantaged persons. In order to learn from the U.S. financial crisis, we have to enforce action by people who see it as their duty to protect the American people. We have to focus as much on the regulators as on the regulations (Krugman, 2010, p. 2). Financial consumers need protection from being taken advantage of or else we will have failed to learn from our recent history and can expect to repeat it again. References Andrews, E. (2009). Busted: Life Inside the Great Mortgage Meltdown. New York, NY: W.W. Norton Company, Inc. Ciulla, J, ed. (2003). The Ethics of Leadership. Belmont, CA: Wadsworth. Cohan, W. (2009). House of Cards: A Tale of Hubris and Wretched Excess on Wall Street. New York, NY: Doubleday Publishing Group. Ghate, O. (2009, June). The Economy Needs Ayn Rand. BusinessWeek. Retrieved February 24, 2010, from businessweek.com/debateroom/archives/2009/04/the_ economy_ nee_1.html Kakutani, M. (2010, March). Investors Who Foresaw the Meltdown. New York Times, March 15. Krugman, P. (2010, March). An Irish Mirror. New York Times, March 8. Marples, G. (2008, September). The History of Home Mortgages. TheHistoryOf. Retrieved February 25, 2010, from thehistoryof.net/history-of-home-mortgages.html Mason, P. (2009). Meltdown: The End of the Age of Greed. London: Verso. Merrel, S. (2009, September). A Thorny Dilemma: The Ethics of Mortgage Walkaways. SmartNestEgg. Retrieved February 27, 2010, from smartnestegg.com/blog/2009/9/4/a- thorny-dilemma-the-ethics-of-mortgage-walkaways.html Muolo, P., Padilla, M. (2008). Chain of Blame: How Wall Street Caused the Mortgage and Credit Crisis. Hoboken, NJ: John Wiley Sons, Inc. Shiller, R. (2008). The Subprime Solution: How Todays Global Financial Crisis Happened, and What to do About it. Princeton, NJ: Princeton University Press. Smith, V. (2009, April). IMF: Mortgage Crisis May Cost $945bn Worldwide. InfiniteUnkwown. Retrieved March 1, 2010, from infiniteunknown.net/2008/04/09/imf- mortgage-crisis-may-cost-945bn-worldwide

Introduction Paper Essay

I am 30 years old and have been taking college courses over the last 11 years. I have always attended on a part time basis and I have never taken any summer courses. During the 11 years I have taken about two years off, and have officially changed my major three times. I have a lot of work experience that lines up with my current Business Management Major. I enjoy learning about Human Resources and have always thought I would enjoy a position in the Human Resources department. Academic Background When I started this journey I wanted to be an accountant, after my first semester at Saint Paul College a I realized, I did NOT want to be an accountant! The classes were very hard and a lot of work, there was just way too much to learn. I had a passion for children and growing up I always wanted to be a teacher, so I switched into a major in Child Development (CD). I made it through about two semesters of CD courses and learned that this was not the right path for me either. The instructors repeatedly reminded the students that careers in the CD field are not about making money (because there is not a lot of money in this field) but rather about working with the children. I thought I DO want to make money and instead of working with kids I would just have some of my own later in life. I also realized that if I completed this program, in the end I would have an education but no work experience. At this point I had no idea what I was going to get a degree in. I looked at my resume and realized that I had experience in operations management, Import/Export, various management positions at fast food restaurants, and extensive customer service experience. I came to the conclusion that a degree in Business Management would benefit me most, as it will ensure I have the education to match the experience. In 2009 I graduated from Saint Paul College with an AA as well as an AS in Business Management and in 2010 I transferred to Metro State University to complete my BS. This Course & Past HR Courses I took an Introduction to Human Resource Management course in 2004 of which I received an A grade, but it did not satisfy this course as required for the completion of my BS in Business Management. Since I have already taken a similar course, I do hope I can obtain another good grade, and possibly learn something I may have overlooked previously. I look forward to hearing the perspectives and ideas on how to handle different situations from the other students. More about Me I have been with my boyfriend for almost 10 years; we have a one year old daughter and plan to try for another after this semester is over. We have three large dogs ranging in age from 6-15, and once had a bearded dragon. We live 45 miles north of the twin cities in Harris – a town of about 1000 people. I work full time at BAE Systems in Fridley as a government property administrator, with previous positions held in Accounts Payable, Travel Accounting, and payroll. Conclusion As you can see my path through college has been a confusing one, and has had its failures and successes. Now that I am on the right path, I hope to be a successful business person. With my customer service and payroll experience, I have always thought I would be a good fit for an HR representative. I am a new mom and eager to expand my family further! I commute to work and have held several positions within the company. I am just an average person working my way through life and trying to obtain an education to make the quality of my life even better.

Persuasive Essay Topics for Middle School Students Reviews & Tips

Persuasive Essay Topics for Middle School Students Reviews & Tips These points illustrate how to compose a persuasive essay step-by-step. On the opposing side, obtaining a list of good persuasive essay topics is insufficient. So locating the most effective persuasive essay topics is critical. You may also have essay samples online on the site. When it has to do with persuasive essays, a topic is among the key things that ought to be considered by all high-school students. In the same way as any other essay, the topic holds the most essential part. You have to settle on a persuasive essay topic that permits you to present the finest possible case. There are a few great topics to look at when picking a topic for your argumentative essay. It is preferable to select the topic you know and the position you believe in. It's needless to say that you should choose a subject that you regard as interesting. To write a fantastic persuasive paper, decide on some controversial subject that you truly feel strongly about. In reality, a great deal of argumentative essays are in reality persuasive papers. Persuasive papers (also called argumentative essays) are possibly the most important academic projects you'll learn how to write. When it's difficult for you to write such a paper, you're able to pick easy persuasive essay topics. An argumentative paper is part of the persuasion. Punishment for cutting school ought to be made much worse. Every school has to have a sex education class. School uniforms should be deemed necessary. They can help with teaching discipline. Schools should not have anything to do with ads. Children watch an excessive amount of television. Some schools in america are requiring that students volunteer for a number of hours each semester to assist on a community issue. Think of one school rule that you truly dislike. Before students begin to write, it is a fantastic idea for them to earn a list of the points they would like to make to their readers. They would be required to brainstorm the pros and cons of allowing cell phones in class. For example, they could choose to argue for the addition of a swimming pool or better school lunches. They often stress about looking for utile persuasive essay tips and searching for ideas because they feel it's an uphill task, but the key is to understand the essence and create a proper outline first by planning for it properly. If you're in a middle school, it is preferable to simplify a topic a little. As soon as you have the topic, answer the question and support your answer with three or more explanations for why you believe it. In speech school, you're supposed to decide on the sort of topic you're going to be in a position to dig into that is, you must remember to can discover enough info on the matter. In high school, you're supposed to decide on the type of topic you'll be in a position to dig into that is, you need to make certain you can come across enough info on the discipline. Students are accustomed to the simple fact which their professors give them with the assignment's topic. In doing so, they would have to think objectively and decide if the addition would benefit everybody or just a select few. Still, in regards to practice, not every student can think of an ideal speech in only a day or two. Many students have a tendency to encounter the writing issues due to the shortage of suitable comprehension.

Utility of lp-pla2 in lipid lowering therapy - Free Essay Example

Sample details Pages: 9 Words: 2696 Downloads: 6 Date added: 2017/06/26 Category Health Essay Type Analytical essay Did you like this example? ABSTRACT Lipoprotein- associated phopholipase A2 (Lp-PLA2) is a vascular-specific inflammatory marker. It is so named because of its association with low-density lipoprotein (LDL) in plasma. Atherosclerosis is an inflammatory disease. Don’t waste time! Our writers will create an original "Utility of lp-pla2 in lipid lowering therapy" essay for you Create order Lp-PLA2 is recognized as a risk marker in primary or secondary prevention of atherosclerosis. Elevated Lp-PLA2 levels are associated with the increased risk for cardiovascular events, even after multivariable adjustment for traditional risk factors. Patients with dyslipidemia are shown to benefit largely from the modification of Lp-PLA2. The degree of CAD (0-, 1-, 2- or 3-vessel disease) and plasma LDL cholesterol significantly correlated to Lp-PLA2 levels. The low biologic fluctuation and high vascular specificity of Lp-PLA2 makes it possible to use a single measurement in clinical decision making, and it also permits clinicians to follow the Lp-PLA2 marker serially. Simvastatin significantly reduces macrophage content, lipid retention and the intima/media ratio but increased the content of smooth muscle cells in atherosclerotic lesions. Statin treatment markedly reduced Lp-PLA2 in both plasma and atherosclerotic plaques with attenuation of the local inflammatory response and improv ed plaque stability due to reduced inflammation and decreased apoptosis of macrophages. Darapladib, an inhibitor of Lp-PLA2, when added to lipid lowering therapy such as statins, offers great benefit in the reduction of plaque formation. This article explores the atherosclerotic process at molecular level, role of Lp-PLA2 in atherosclerosis, the effect of lipid lowering drugs on Lp-PLA2, effect of direct Lp-PLA2 inhibitor darapladib in the atherosclerosis process, the therapeutic implications of Lp-PLA2 as risk marker, and finally, the net effect on plaque stabilization. Utility of Lp-PLA2 in lipid lowering therapy Introduction: Atherosclerosis is an inflammatory disease. Lp-PLA2 is recognized as a risk marker in primary or secondary prevention of atherosclerosis. Lp-PLA2 is so named because of its association with LDL in plasma1. Lp-PLA2 is also known as low density associated platelet-activating factor acetyl-hydrolase (PAF-AH) 2. Patients with dyslipidemia are shown to benefit largely from the modification of Lp-PLA23. Understanding the mechanism of atherosclerotic process is essential in knowing the utility of Lp-PLA2 in lipid lowering therapy. Inflammatory markers of atherosclerosis: Lp-PLA2 is a vascular-specific inflammatory marker4. Others include C-reactive protein (CRP), myeloperoxidase, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). Serum Lp-PLA2 level has higher sensitivity in predicting the vulnerability of the coronary atherosclerotic plaque than CRP5. Phospholipase inhibitors in atherosclerosis: The secreted PLA2 and Lp-PLA2 have been associated with a therogenesis and its complications. These two enzymes produce biologically active metabolites that are involved in several phases of the atherosclerosis process6. Structure of LDL: Low density lipoprotein (LDL) particles are the major cholesterol carriers in circulation and their physiological function is to carry cholesterol to the cells. In the process of atherogenesis these particles are modified and they accumulate in the arterial wall. LDL is a three-layer particle with outer surface, interfacial layer, and core. This structural information is utilized to understand and explain the molecular characteristics and interactions of modified, atherogenic LDL particles7. Phospholipids such as phophatidylcholine are located on the outersurface of LDL8. Phospholipid transfer protein (PLTP) was found to mediate transfer of anionic phospholipids to HDL and LDL, thereby neutralizing the effect of procoagulant liposomes resulting in a reduction of procoagulant activity9. Action of Lp-PLA2: It is an enzyme that catalyzes the hydrolysis of oxidized phopholipids on LDL to lyso-phospholipid and oxidized fatty acids in the atherosclerotic plaque (See figure 1). Infl ammatory and Immunologic process in Atherosclerosis: It appears that Lp-PLA2 is released from the macrophages of atherosclerotic plaques into the circulation. A recent study showed a significant correlation between PLA2G7 RNA expression in plaque macrophages and plasma PAF-AH activity, which suggests that the latter is a consequence, rather than a cause of macrophage accumulation. It was also noticed that oxidized LDL can induce PAFAH, resulting in accumulation of lysophosphatidylcholine that increases the inflammatory action of oxidized LDL10, 11. Endothelial dysfunction is the earliest step in the atherosclerosis. Endothelial senenscence is brought about by various stress factors which include endothelial injury, NO depletion, and free radicals etc12. Molecules, such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin, support the adhesion of monocytes and lymphocytes to the endothelium. LDL undergoes oxidation by the oxygen fr ee radical released from the macrophages. Oxidation of LDL at the sites of endothelial damage is thought to be a major stimulus for uptake by macrophages, as oxidized LDL is considered to be autoantigen13. Lectin-like oxidized LDL receptor (LOX)-1 and scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX) are type II and I membrane glycoproteins, respectively, both of which can act as cell-surface endocytosis receptors for atherogenic oxidized LDL 14. Phagocytosis into macrophages through these scavenger receptors, causes the production of cytokines like Tumoral Necrosis Factor (TNF)- alpha, Interleukin (IL)-1 beta, IL-6, IL-12 and IL-18, among others. This secretion generates T cells activation into T helper lymphocytes (Th1), able to recognize the oxidised LDL and heat shock protein as autoantigens, amplifying the inflammatory response15. Lp-PLA2 hydrolyzes oxidized phospholipids in LDL to produce biologically active lysophosphatidylcholine and oxidized nones terified fatty acids which contribute to atherosclerotic plaque instability and subsequent sudden coronary death16. Lysophosphotidyl choline activates several second messengers including protein kinase C, extracellular-signal-regulated kinases, protein tyrosine kinases, and Ca(2+) with a range of potentially atherogenic effects, including chemoattraction of monocytes, increased expression of adhesion molecules, and inhibition of endothelial nitric oxide production17. A critical event in the early stages of atherosclerosis is the focal accumulation of lipid-laden foam cells derived from macrophages. These foam cells tend to accumulate in the intimal layer of vascular wall. Death of macrophages and smooth muscle cells (SMC) can lead to progression of atherosclerosis18. The hydrolysis products of oxidised phospholipids may account for these cytotoxic and apoptosis-inducing effects on macrophages19. Defects in failure to resolve inflammation (which normally involves the suppression of inflammatory cell influx, effective clearance of apoptotic cells and promotion of inflammatory cell egress) promote the progression of atherosclerotic lesions into dangerous plaques20 (See figure 2). Lipid Lowering action of Statin: Cholesterol is known to participate in atheromatous plaque formation coming from blood stream and affecting vascular endothelium in environment of elevated LDL21. HMG-CoA reductase inhibitors (statins) are believed to inhibit cholesterol synthesis by inhibiting the following pathway and contribute to decreased LDL (See figure 3). Decreased cholesterol in the liver causes an upregulation of LDL receptors on the hepatocyte cell membrane, consequently, leading to the reduction in blood LDL levels. Statins decrease of LDL cholesterol and increase of HDL cholesterol slows down the evolution of atherosclerosis, stabilizes the atherosclerotic plaques, and even brings about their partial regression22. Pleiotropic action of statin on plaque: Statin s ignificantly reduces macrophage content, lipid retention and the intima/media ratio but increased the content of smooth muscle cells in atherosclerotic lesions. As Lp-PLA2 is considered to be releasing from the macrophages, reduction of macrophage has a significant effect in the formation of Lp-PLA223. Certain statins bind adhesion molecules, including functional leukocytic antigen-1, and therefore block their interaction with T lymphocytes and macrophages expressing the counter-receptor intercellular adhesion molecule-1 (ICAM-1)24. HMG-CoA reductase inhibitor, retards the initiation of atherosclerosis process through the improvement of NO bioavailability by both up-regulation of endothelial nitric oxide synthase mRNA and decrease of O(2)(-) production in vascular endothelial cells25. Bone marrow derived endothelial progenitor cells (EPCs) are early precursors of mature endothelial cells which replenish aging and damaged endothelial cells. DM results in significant impairme nt of bone marrow and circulating EPCs as well as endothelial function. The effect is ameliorated, in part, by atorvastatin independent of its cholesterol lowering effect. These data suggest a model wherein accelerated atherosclerosis seen with DM may, in part, result from reduction in EPCs which may be ameliorated by treatment with a statin26, 27. Oxidized low-density lipoprotein (oxLDL) is immunogenic. A recent study had determined the autoantibody titers against various forms of oxLDL in patients with acute coronary syndromes without persistent elevation of the ST segment (NSTE-ACS) and suggested an important role of the LDL-associated Lp-PLA(2) in modulating these immune responses. Moreover, the effect of early atorvastatin administration on these autoantibody titers was evaluated. From the 133 consecutive NSTE-ACS patients, 55 were eligible for the study. Thirty-four received atorvastatin (group A), whereas 21 did not received any hypolipidemic therapy (group B). Two forms o f copper-oxidized LDL were prepared at the end of propagation or decomposition phase (oxLDL(P) or oxLDL(D), respectively). Similar types of oxLDL were prepared after previous inactivation of the endogenous Lp-PLA(2) [oxLDL(-)]. In group B, autoantibody titers of IgG class against oxLDL(P) and oxLDL(D) were elevated at 1 month of follow-up to reach the baseline values 3 months afterwards. By contrast the titers against oxLDL(-)(P) and oxLDL(-)(D) increased at 1 month of follow-up and remained elevated for up to 6 months of follow-up. Atorvastatin treatment prevented the elevation of autoantibody titers against all forms of oxidized LDL. We conclude that a short-term immune response against oxLDL(P) and oxLDL(D) (enriched in lyso-PC) and a chronic immune response against oxLDL(-)(P) and oxLDL(-)(D) (enriched in oxPL) are observed after an NSTE-ACS, suggesting an important role of the LDL-associated Lp-PLA(2) in modulating these immune responses. Early atorvastatin treatment prevents b oth immune responses; however, the clinical significance of this effect remains to be established28. Thus, statin treatment markedly reduced Lp-PLA2 in both plasma and atherosclerotic plaques with attenuation of the local inflammatory response and improved plaque stability 29-33. Effect of direct Lp-PLA2 inhibiton: Darapladib, an inhibitor of Lp-PLA2, when added to lipid lowering therapy such as statins, prevents necrotic core expansion and offers great benefit in the reduction of plaque formation34. Darapladib is an orally available, specific inhibitor of LpPLA2 activity and has been shown to reduce lysophosphatidylcholine content and expression of multiple genes associated with macrophage and T-lymphocyte functioning, with considerable decrease in plaque and necrotic core area35. The potential plaque-stabilizing effects of darapladib may represent an important approach in treating atherosclerosis and reducing cardiovascular risk (See figure 4) Therapeutic interpretation o f Lp-PLA2 as an inflammatory risk marker: The degree of CAD (0-, 1-, 2- or 3-vessel disease) and plasma LDL cholesterol significantly correlated to Lp-PLA2 levels36. Elevated Lp-PLA2 levels is associated with the increased risk for cardiovascular events, even after multivariable adjustment for traditional risk factors. Patients with dyslipidemia are shown to benefit largely from the modification of Lp-PLA2 37. The low biologic fluctuation and high vascular specificity of Lp-PLA2 makes it possible to use a single measurement in clinical decision making, and it also permits clinicians to follow the Lp-PLA2 marker serially38. Lp-PLA2 is a therapeutic target even in post-transplant patients39. Patients with 30-day Lp-PLA2 activity in the highest quintile were at significantly increased risk of recurrent CV events compared with those in the lowest quintile. Lp-PLA2 is not useful for risk stratification when measured early after ACS. At 30 days, Lp-PLA2 activity is significantly lowered w ith high-dose statin therapy40. Lp-PLA2 is a significant and independent predictor of risk even for recurrent coronary events in post-infarction patients41. Recent study shows emerging evidence from more than 15 prospective studies conducted since 2000, clearly demonstrate the prognostic ability of increased Lp-PLA2 concentrations or elevated activity for risk of future coronary heart disease (CHD) and stroke 48. Future of Lp-PLA2 as a therapeutic target in various disorders in addition to acute coronary syndrome: A recent prospective study was done to investigate Lp-PLA2 levels in patients with ischemic stroke and severe inflammatory reaction as compared to 38 patients with ischemic stroke without inflammatory reaction and healthy elderly controls. Lp-PLA2 levels were assessed using the diaDexus PLAC test (a noncompetitive ELISA. Patients with ischemic stroke and severe inflammatory reaction presented Lp-PLA2 with high levels more frequently than the healthy controls. Lp-PLA2 is a strong predictor of recurrent stroke risk and of increased risk of dying. The determination of Lp-PLA2 should be used to predict patient risk of cardiovascular disease and stroke. Lp-PLA2 might be used not only for risk stratification of stroke patients, but also as target for treatment42. PAF-AH activity and distribution in women with polycystic ovarian syndrome (PCOS) could contribute to the low-grade chronic inflammation and increased risk of atherosclerosis43. Laboratory of genetic disease and perinatal med icine, conducted a study to investigate a possible association of the polymorphism of PAF-AH gene with the risk of PCOS and to evaluate the effects of the genotype on the activity and distribution of PAFAH. Prevalence of the mutant genotype (GT + TT) was significantly more frequent in patients with PCOS than in control subjects. Genotype (GT + TT) remained a significant predictor for PCOS in prognostic models including age, body mass index, insulin resistance index, triglyceride, HDL and LDL as covariates. The G994T polymorphism in PAFAH gene may be one of the genetic determinants for PCOS 49. A recent data supports an association between deficiency in PAFAH activity and atopic asthma 44. Platelet-activating factor (PAF), which has been implicated in the pathophysiology of inflammation in asthma, is degraded and inactivated by PAF acetylhydrolase (PAFAH. Deficiency of PAFAH is due to a loss-of-function variant (Val279Phe) in the PAFAH gene.50 Inflammation may be a causative fa ctor in congestive heart failure (CHF). In a Cardiovascular Health Study, a prospective observational study demonstrated an association of Lp-PLA2 antigen with risk of future CHF in older people, independent of CHF and coronary risk factors, and partly mediated by coronary disease events45. PAF-AH is been shown to be positively correlated with an increase C-reactive protein in Diabetes type 1 (DM1) patients. PAF-AH appears to be implicated in the development of a chronic inflammation in DM1. This was found by evaluating the concentration of PAF-AH in patients treated with intensive insulin therapy in DM1 46. In a Health Professionals Follow-up Study (HPFS) and Nurses Health Study (NHS), it is found the levels of Lp-PLA2 activity were significantly associated with incident CHD among men and women with type 2 diabetes, independent of traditional and inflammatory risk factors 51. In summary: Lipid lowering agents especially statins decrease LDL level and inhibit Lp-PLA2, which reduces plaque formation and increases plaque stability due to reduced inflammation and decreased apoptosis of macrophages47. Darapladib, a direct inhibitor of Lp-PLA2, when added to lipid lowering therapy such as statins, offers great benefit through the potential plaque-stabilizing effect. Lp-PLA2 as an inflammatory marker, it is used as therapeutic target of lipid lowering drugs and could be utilized for pre-treatment risk assessment and post-treatment monitoring. References:- 1. 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