Inhibition of sPLA2-IIA, C-reactive protein or complement: new therapy for patients with acute myocardial infarction?
Reperfusion of ischemic myocardium after acute myocardial infarction (AMI) induces a local activation of inflammatory reactions that results in ischemia/reperfusion (I/R)-injury. I/R-injury contributes considerably to the total cell damage in the heart after AMI. Secretory phospolipase A2-IIA (sPLA2-IIA), C-reactive protein (CRP) and complement are inflammatory mediators that have been demonstrated to play key roles in I/R injury. From studies by us and others a mechanism emerged in which sPLA2-IIA binds to reversibly damaged cardiomyocytes and subsequently induces cell death, partly by potentiating binding of CRP and subsequent complement activation. Next to this, sPLA2-IIA also has a direct toxic effect, independent of CRP or complement. Therefore, these studies indicate a crucial role of inflammatory mediators in ischemia/reperfusion injury. This review will focus on the pathogenic effects of sPLA2-IIA, CRP and complement and on the putative therapeutic effects of inhibitors of these inflammatory mediators in acute myocardial infarction.
Krijnen
Paul A J
PA
VU Medical Center, Department of Pathology, Room nr. 1B116, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands. paj.krijnen@vumc.nl
Meischl
Christof
C
Nijmeijer
Remco
R
Visser
Cees A
CA
Hack
C Erik
CE
Niessen
Hans W M
HW
D000818:Animals; D002097:C-Reactive Protein / Q000037:antagonists & inhibitors*; D051056:Complement Inactivating Agents / Q000494:pharmacology; D003165:Complement System Proteins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054501:Group II Phospholipases A2; D006801:Humans; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D010741:Phospholipases A / Q000037:antagonists & inhibitors*
D051056:Complement Inactivating Agents; D004791:Enzyme Inhibitors; D003165:Complement System Proteins; D002097:C-Reactive Protein; D010741:Phospholipases A; D054501:Group II Phospholipases A2