Lipoprotein-associated phospholipase A2: role in atherosclerosis and utility as a cardiovascular biomarker.
Atherosclerosis and its clinical manifestations are widely prevalent throughout the world. Atherogenesis is highly complex and is modulated by numerous genetic and environmental risk factors. A large body of basic scientific and clinical research supports the conclusion that inflammation plays a significant role in atherogenesis along the entire continuum of its progression. Inflammation adversely impacts intravascular lipid handling and metabolism, resulting in the development of macrophage foam cells, fatty streaks and atheromatous plaque formation. Given the enormous human and economic cost of myocardial infarction, ischemic stroke, peripheral arterial disease and amputation, and premature death and disability, considerable effort is being committed to refining our ability to correctly identify patients at heightened risk for atherosclerotic vascular disease and acute cardiovascular events so that they can be treated earlier and more aggressively. Serum markers of inflammation have emerged as an important component of risk factor burden. Serum lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) potentiates intravascular inflammation and atherosclerosis. A variety of epidemiologic studies support the utility of Lp-PLA(2) measurements for estimating and further refining cardiovascular disease risk. Drug therapies to inhibit Lp-PLA(2) are in development and show considerable promise. In addition to substantially inhibiting Lp-PLA(2), darapladib reduces the progression of the necrotic core volume of coronary artery atheromatous plaque.
Toth
Peter P
PP
Sterling Rock Falls Clinic, 101 East Miller Road, Sterling, IL 61081, USA. peter.toth@srfc.com
McCullough
Peter A
PA
Wegner
Michael S
MS
Colley
Kenneth J
KJ
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000032:analysis / Q000378:metabolism*; D050197:Atherosclerosis / Q000097:blood* / Q000201:enzymology / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D011379:Prognosis; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016019:Survival Analysis
D015415:Biomarkers; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase