Inhibition of vascular peroxidase alleviates cardiac dysfunction and apoptosis induced by ischemia-reperfusion.
Myeloperoxidase (MPO) is involved in myocardial ischemia-reperfusion (IR) injury and vascular peroxidase (VPO) is a newly identified isoform of MPO. This study was conducted to explore whether VPO is involved in IR-induced cardiac dysfunction and apoptosis. In a rat Langendorff model of myocardial IR, the cardiac function parameters (left ventricular pressure and the maximum derivatives of left ventricular pressure and coronary flow), creatine kinase (CK) activity, apoptosis, VPO1 activity were measured. In a cell (rat-heart-derived H9c2 cells) model of hypoxia-reoxygenation (HR), apoptosis, VPO activity, and VPO1 mRNA expression were examined. In isolated heart, IR caused a marked decrease in cardiac function and a significant increase in apoptosis, CK, and VPO activity. These effects were attenuated by pharmacologic inhibition of VPO. In vitro, pharmacologic inhibition of VPO activity or silencing of VPO1 expression significantly suppressed HR-induced cellular apoptosis. Our results suggest that increased VPO activity contributes to IR-induced cardiac dysfunction and inhibition of VPO activity may have the potential clinical value in protecting the myocardium against IR injury.
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, PR China.
Ting-Ting
TT
Li
Yi-Shuai
YS
Zhang
Lan
L
He
Bin
B
Liu
Rui-Zheng
RZ
Shi
Guo-Gang
GG
Zhang
Jun
J
Peng
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006331:Heart Diseases / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006420:Hemeproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008297:Male; D015425:Myocardial Reperfusion / Q000379:methods; D015428:Myocardial Reperfusion Injury / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D010544:Peroxidases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010696:Phloroglucinol / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D006420:Hemeproteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D010696:Phloroglucinol; C573339:vascular peroxidase, rat; D010544:Peroxidases; D002374:Catalase; D009195:Peroxidase; D003402:Creatine Kinase