Abstract
Inflammation lies at the base of endothelial dysfunction, eventually leading to plaque formation. The degree of inflammation defines the “vulnerability” of plaque to rupture. Numerous strategies have been adopted to identify and eventually treat high-risk vulnerable plaque. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has emerged as one such candidate marker of inflammation that may play a direct role in the formation of rupture-prone plaque. Epidemiologic studies have clearly demonstrated the prognostic ability of increased Lp-PLA2 levels and their association with increased risk of future coronary and cerebrovascular events. Moreover, Lp-PLA2 might have similar predictive power for both incident coronary heart disease in initially healthy individuals as well as for recurrent events in those with clinically manifest atherosclerosis. The latest evidence has also suggested its incremental value for risk determination over the well-established traditional risk factors and biomarkers in patients with congestive heart failure. These data support an integral role of Lp-PLA2 activity in lipid peroxidation and cardiovascular risk assessment. This review summarizes the current body of evidence supporting the clinical utility of Lp-PLA2 and its future applications in cardiovascular medicine.
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Kolodgie FD, Burke AP, Skorija KS et al.: Lipoprotein-associated phospholipase A2 protein expression in the natural progression of human coronary atherosclerosis. Arterioscler Thromb Vasc Biol 2006, 26:2523–2529.
Carpenter KL, Dennis IF, Challis IR, et al.: Inhibition of lipoprotein-associated phospholipase A2 diminishes the death-inducing effects of oxidised LDL on human monocyte-macrophages. FEBS Lett 2001, 505:357–363.
Quarck R, De Geest B, Stengel D, et al.: Adenovirus-mediated gene transfer of human platelet-activating factor-acetylhydrolase prevents injury-induced neointima formation and reduces spontaneous atherosclerosis in apolipoprotein E–deficient mice. Circulation 2001, 103:2495–2500.
• Tsimikas S, Tsironis LD, Tselepis AD: New insights into the role of lipoprotein(a)-associated lipoprotein-associated phospholipase A2 in atherosclerosis and cardiovascular disease. Arterioscler Thromb Vasc Biol 2007, 27:2094–2099. This article outlines the key role of Lp-PLA 2 in initiation and progression of atherosclerosis and CAD.
Chen CH: Platelet-activating factor acetylhydrolase: is it good or bad for you? Curr Opin Lipidol 2004, 15:337–341.
Stafforini DM, Satoh K, Atkinson DL, et al.: Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase. J Clin Invest 1996, 97:2784–2791.
Ishihara M, Iwasaki T, Nagano M, et al.: Functional impairment of two novel mutations detected in lipoprotein-associated phospholipase A2 (Lp-PLA2) deficiency patients. J Hum Genet 2004, 49:302–307.
Abuzeid AM, Hawe E, Humphries SE, et al., for the HIFMECH Study Group: Association between the Ala379Val variant of the lipoprotein associated phospholipase A2 and risk of myocardial infarction in the north and south of Europe. Atherosclerosis 2003, 168:283–288.
Brilakis ES, Joseph P, et al.: Association of lipoprotein-associated phospholipase A2 levels with coronary artery disease risk factors,angiographic coronary artery disease, and major adverse events at follow-up. Eur Heart J 2005, 26:137–144.
Caslake MJ, Packard CJ, Suckling KE, et al.: Lipoprotein-associated phospholipase A(2), platelet-activating factor acetylhydrolase: a potential new risk factor for coronary artery disease. Atherosclerosis 2000, 150:413–419.
Oei H-H, van der Meer IM, Hofman A, et al.: Lipoprotein-associated phospholipase a2 activity is associated with risk of coronary heart disease and ischemic stroke: the Rotterdam Study. Circulation 2005, 111:570–575.
Kiechl S, Willeit J, Mayr M, et al.: Oxidized phospholipids,lipoprotein(a), lipoprotein-associated phospholipase A2 activity, and 10-year outcomes: prospective results from the Bruneck study. Arterioscler Thromb Vasc Biol 2007, 27(8):1788–1795.
Suzuki T, Solomon C, Jenny NS, et al.: Lipoprotein-associated phospholipase A(2) and risk of congestive heart failure in older adults: the Cardiovascular Health Study. Circ Heart Fail 2009, 2:429–436.
Gerber Y, McConnell JP, Jaffe AS, et al.: Lipoprotein-associated phospholipase A2 and prognosis after myocardial infarction in the community. Arterioscler Thromb Vasc Biol 2006, 26:2517–2522.
•• Garza CA, Montori VM, McConnell JP, et al.: Association between lipoprotein-associated phospholipase A2 and cardiovascular disease: a systematic review. Mayo Clin Proc 2007, 82:159–165. This article outlines the importance of Lp-PLA 2 and its role in CVD.
Iribarren C, Gross MD , Darbinian JA, et al.: Association of lipoprotein-associated phospholipase A2 mass and activity with calcified coronary plaque in young adults: the CARDIA study. Arterioscler Thromb Vasc Biol 2005, 25:216–221.
MacPhee CH: Lipoprotein-associated phospholipase A2: a potential new risk factor for coronary artery disease and a therapeutic target. Curr Opin Pharmacol 2001, 1:121–125.
Boyd HF, Fell SC, Hickey DM, et al.: Potent, orally active inhibitors of lipoprotein-associated phospholipase A(2): 1-(biphenylmethylamidoalkyl)-pyrimidones. Bioorg Med Chem Lett 2002, 12:51–55.
Sudhir K: Clinical review: lipoprotein-associated phospholipase A2, a novel inflammatory biomarker and independent risk predictor for cardiovascular disease. J Clin Endocrinol Metab 2005, 90:3100–3105.
• Serruys PW, Garcia-Garcia HM, Buszman P, et al.: Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque. Circulation 2008, 118:1172–1182. This article outlines the direct inhibition of Lp-PLA 2 using darapladib and its effect of plaque progression.
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Bhatti, S., Hakeem, A. & Cilingiroglu, M. Lp-PLA2 as a Marker of Cardiovascular Diseases. Curr Atheroscler Rep 12, 140–144 (2010). https://doi.org/10.1007/s11883-010-0095-6
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DOI: https://doi.org/10.1007/s11883-010-0095-6