Type II secretory phospholipase A2 binds to ischemic flip-flopped cardiomyocytes and subsequently induces cell death.
Type II secretory phospholipase A2 (sPLA2) is a cardiovascular risk factor. We recently found depositions of sPLA2 in the necrotic center of infarcted human myocardium and normally appearing cardiomyocytes adjacent to the border zone. The consequences of binding of sPLA2 to ischemic cardiomyocytes are not known. To explore a potential effect of sPLA2 on ischemic cardiomyocytes at a cellular level we used an in vitro model. The cardiomyocyte cell line H9c2 or adult cardiomyocytes were isolated from rabbits that were incubated with sPLA2 in the presence of metabolic inhibitors to mimic ischemia-reperfusion conditions. Cell viability was established with the use of annexin V and propidium iodide or 7-aminoactinomycin D. Metabolic inhibition induced an increase of the number of flip-flopped cells, including a population that did not stain with propidium iodide and that was caspase-3 negative. sPLA2 bound to the flip-flopped cells, including those negative for caspase-3. sPLA2 binding induced cell death in these latter cells. In addition, sPLA2 potentiated the binding of C-reactive protein (CRP) to these cells. We conclude that by binding to flip-flopped cardiomyocytes, including those that are caspase-3 negative and presumably reversibly injured, sPLA2 may induce cell death and tag these cells with CRP.
Nijmeijer
R
R
Vrije Universiteit Medical Center, Department of Pathology, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands.
Willemsen
M
M
Meijer
C J L M
CJ
Visser
C A
CA
Verheijen
R H
RH
Gottlieb
R A
RA
Hack
C E
CE
Niessen
H W M
HW
D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D054501:Group II Phospholipases A2; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000201:enzymology*; D010741:Phospholipases A / Q000378:metabolism* / Q000494:pharmacology; D054467:Phospholipases A2; D011817:Rabbits; D051381:Rats
D002614:Chelating Agents; D004533:Egtazic Acid; D002097:C-Reactive Protein; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2; D002118:Calcium