Phospholipase A2 enzymes and the risk of atherosclerosis.
Certain members of the phospholipase A(2) superfamily of enzymes have established causal involvement in atherosclerosis, thus at least two groups of this family of enzymes have been considered potential candidates for the prevention of cardiovascular events. Recently completed experimental animal studies, human biomarker data, vascular imaging studies, and genome-wide atherosclerosis studies provide the rationale for proceeding with clinical outcome trials directed at inhibition of secretory phospholipase A(2) and lipoprotein-associated phospholipase A(2). A clinical trial with the sPLA(2) inhibitor varespladib methyl was recently terminated, while clinical trials with the Lp-PLA(2) inhibitor darapladib are being conducted in coronary heart disease patients. This article reviews the available experimental animal and human trial evidence that serve as the basis for the development of these two classes of phospholipase A(2) inhibitors.
Mount Sinai School of Medicine, 1425 Madison Ave., Box 1030, New York, NY 10029, USA. robert.rosenson@mssm.edu
Robert S
RS
Rosenson
Eva
E
Hurt-Camejo
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D000085:Acetates / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000201:enzymology*; D001547:Benzaldehydes / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000201:enzymology; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006168:Guinea Pigs; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D007651:Keto Acids; D051379:Mice; D020125:Mutation, Missense / Q000235:genetics; D017202:Myocardial Ischemia / Q000201:enzymology; D032383:Myocytes, Cardiac / Q000201:enzymology; D010091:Oximes / Q000494:pharmacology / Q000627:therapeutic use; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors; D001713:Biphenyl Compounds; D004048:Diethylamines; D011744:Pyrimidinones; D013440:Sulfides
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000085:Acetates; D001547:Benzaldehydes; D015415:Biomarkers; D004791:Enzyme Inhibitors; D007211:Indoles; D007651:Keto Acids; D010091:Oximes; D054497:Phospholipases A2, Secretory; C545088:varespladib methyl; C529040:darapladib; D001713:Biphenyl Compounds; D004048:Diethylamines; D011744:Pyrimidinones; D013440:Sulfides