Phospholipase A2 inhibitors.
OBJECTIVE
As the role of lipids and inflammation in the genesis and progression of the atherosclerosis disease is unquestionable, novel treatment modalities that target both aspects are currently under investigation.


RESULTS
For a long time atherosclerosis was regarded as a lipid-driven disease, but now it is evident that it also involves the simultaneous and combined effect of inflammation and immunological pathways. The secreted PLA2s and the lipoprotein-associated phospholipase A2 (Lp-PLA2) have been associated with atherogenesis and its complications. These two enzymes produce biologically active metabolites that are involved in several phases of the atherosclerosis process.


CONCLUSIONS
In animal, pathological and epidemiological studies, the increased levels of these two phospholipases (i.e. PLA2s and Lp-PLA2) have been related with an increase in complex coronary lesions and increase in major cardiovascular clinical events, respectively. Therefore, inhibition of these enzymes has become the focus of research in this last decennium. Novel pharmacological inhibitors of those enzymes such as darapladib and varespladib emerge as promising therapeutical options for treating patients with coronary artery disease. Ongoing mechanistic and clinical outcome trials will further elucidate their role in this context.
Garcia-Garcia
Hector M
HM
Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands.
Serruys
Patrick W
PW
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000037:antagonists & inhibitors*; D000085:Acetates / Q000627:therapeutic use; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism; D001547:Benzaldehydes / Q000627:therapeutic use; D001798:Blood Proteins / Q000627:therapeutic use*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy; D007651:Keto Acids; D010091:Oximes / Q000627:therapeutic use; D001713:Biphenyl Compounds; D004048:Diethylamines; D011744:Pyrimidinones; D013440:Sulfides
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000085:Acetates; D001547:Benzaldehydes; D001798:Blood Proteins; D007211:Indoles; D007651:Keto Acids; D010091:Oximes; C400481:PLIalpha; C117948:varespladib; C529040:darapladib; D001713:Biphenyl Compounds; D004048:Diethylamines; D011744:Pyrimidinones; D013440:Sulfides