Abstract 3276: Cardiomyocyte-Derived Adiponectin is Biologically Active in Protecting Myocardial Ischemia/Reperfusion Injury
Adiponectin (APN) has traditionally been viewed as an adipocyte-specific endocrine molecule with cardioprotective effects. Recent studies suggest that APN is also expressed in cardiomyocytes. However, biological significances of this locally produced APN remain completely unknown. Adult cardiomyocytes from wild type littermates (WT) or gene deficient mice were pre-treated with vehicle (V) or rosiglitazone (RSG) for 2h followed by simulated ischemia/reperfusion (SI/R, 3h/6h). Compared to WT, myocytes from APN−/− mice sustained greater SI/R injury, evidenced by greater superoxide/peroxynitrite formation, caspase-3 activity and LDH release (P<0.05). Myocytes from APN receptor 1 (APNR1) or APNR1/2 double-deficient mice had slightly increased SI/R injury, but the difference was not statistically significant. RSG significantly increased APN mRNA/protein expression (3.14- and 3.95-fold over V, respectively, P<0.01), upregulated APNR1/2 expression (1.86- and 1.58-fold, P<0.01), reduced SI/R-induced apoptosis (caspase-3 activity: 3.01±0.22 vs. 5.76±0.31 nmol pNA/h/mg protein in V group, P<0.01), and decreased LDH release (32.4±3.9% vs. 59.6±3.5%, P0.05; LDH release: 65.7±4.3% vs. 69.6±4.1%, P>0.05) in cells from APN−/− mice, although a comparable degree of APNR1/2 upregulation was observed. APNR1/2 double-deficiency had no effect on RGS upregulation of APN mRNA/protein expression (3.51- and 3.88-fold, P<0.01 vs. V). However, the cellular protective effects of RSG were significantly blunted, but not completely lost, in these cells (caspase-3 activity: 4.85±0.28 vs. 5.88±0.30 nmol pNA/h/mg protein in V group, P<0.05; LDH release: 51.5±3.7% vs. 62.3±4.1% P<0.05). These results demonstrated for the first time that APN of cardiomyocyte origin is biologically active in protecting cells against SI/R injury. Moreover, this locally produced APN achieves its protective effect primarily through paracrine/autocrine activation of APNRs, and furthermore, a yet to be identified receptor-independent pathway exists.
This research has received full or partial funding support from the American Heart Association, Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).