Lipoprotein-associated phospholipase A2 as a biomarker of coronary heart disease and a therapeutic target.
OBJECTIVE
Lipoprotein-associated phospholipase A2 (Lp PLA2) is postulated to occupy a key position in the pathogenic sequence leading to formation of complex atherosclerotic lesions. This study reviews evidence supporting its role as a biomarker of vascular disease and as a possible therapeutic target.


RESULTS
Evidence continues to build supporting the usefulness of Lp PLA2 as a predictor of coronary events in the general population and in those with established coronary heart disease. Elevated Lp PLA2 is also associated with stroke and heart failure. The crystal structure of Lp PLA2 is now available and offers insight into the links between structure, function and atherogenic properties. Recently completed studies on the efficacy of darapladib, a specific Lp PLA2 inhibitor, show beneficial changes in plaque morphology in animal models and in humans.


CONCLUSIONS
Lp PLA2 is gaining acceptance as a useful biomarker of chronic inflammation and as a predictor of vascular disease. Early results with darapladib offer promise, but not definitive proof, of a potential role for Lp PLA2 inhibition in coronary heart disease prevention.
Department of Vascular Biochemistry, Glasgow Royal Infirmary, Glasgow, Scotland, UK. chris.packard@clinmed.gla.ac.uk
Chris J
CJ
Packard
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001547:Benzaldehydes / Q000627:therapeutic use; D015415:Biomarkers; D008076:Cholesterol, HDL / Q000187:drug effects; D008078:Cholesterol, LDL / Q000187:drug effects; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000201:enzymology / Q000453:epidemiology; D006801:Humans; D007249:Inflammation; D010091:Oximes / Q000627:therapeutic use; D011379:Prognosis; D012307:Risk Factors; D020521:Stroke / Q000201:enzymology / Q000517:prevention & control; D014481:United States / Q000453:epidemiology; D001713:Biphenyl Compounds; D004048:Diethylamines; D011744:Pyrimidinones; D013440:Sulfides
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000893:Anti-Inflammatory Agents; D001547:Benzaldehydes; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D010091:Oximes; C529040:darapladib; D001713:Biphenyl Compounds; D004048:Diethylamines; D011744:Pyrimidinones; D013440:Sulfides