Hyperhomocysteinemia abrogates fasting-induced cardioprotection against ischemia/reperfusion by limiting bioavailability of hydrogen sulfide anions

Elevated plasma homocysteine levels are considered an independent risk factor for cardiovascular diseases. Experimental evidence has shown that hydrogen sulfide anion (HS − )p rotects the myocardium from ischemia/reperfusion (IR) injury. Both homocysteinelevels and endogenousHS − production are mainly regulated by two transsulfuration enzymes, cystathionine βsynthase (CBS) and cystathionine γ-lyase (CTH). We hypothesized that the transsulfuratio np athway plays essential roles in the development of cardiac adaptive responses against ischemia, and investigated the roles of homocysteine, HS − , and transsulfuration enzymes in fasting-induced cardioprotection against IR injury utilizing hyperhomocysteinemic Cbs −/− and Cth −/− mice. Langendorff-perfused hearts were subjected to 25min global ischemia, followed by 60-min reperfusion. Two-day fastingamelioratedleftventriculardysfunctionafterreperfusion