Caveolin-1 peptide exerts cardioprotective effects in myocardial ischemia-reperfusion via nitric oxide mechanism
Caveolin-1 is a protein constituent of cell membranes. The caveolin-1 scaffolding region (residues 82-101) is a known inhibitor of protein kinase C. Inhibition of protein kinase C results in maintained nitric oxide (NO) release from the endothelium, which attenuates cardiac dysfunction after ischemia-reperfusion (I/R). Therefore, we hypothesized that the caveolin-1 scaffolding region of the molecule, termed caveolin-1 peptide, might attenuate postischemia polymorphonuclear neutrophil (PMN)-induced cardiac dysfunction. We examined the effects of caveolin-1 peptide in isolated ischemic (20 min) and reperfused (45 min) rat hearts reperfused with PMNs. Caveolin-1 peptide (165 or 330 µg) given intravenously 1 h before I/R significantly attenuated postischemic PMN-induced cardiac dysfunction, as exemplified by left ventricular developed pressure (LVDP) (P < 0.01) and the maximal rate of develped pressure (+dP/dtmax) (P < 0.01), compared with UR hearts obtained from rats given 0.9% NaCl. In addition, caveolin-1 peptide significantly reduced cardiac PMN infiltration from 195 ± 5 PMNs/mm2 in untreated hearts to 103 ± 5 and 60 ± 5 PMNs/mm2 in hearts from 165 and 330 µg caveolin-1 peptide-treated rats, respectively (P < 0.01). PMN adherence to the rat coronary vasculature was also significantly reduced in rats given either 165 or 330 µg caveolin-1 peptide compared with rats given 0.9% NaCl (P < 0.01). Moreover, caveolin-1 peptide-treated rat aortas exhibited a 2.2-fold greater basal release of NO than vehicle-treated aortas (P < 0.01), and this was inhibited by NG-nitro-L-arginine methyl ester. These results provide evidence that caveolin-1 peptide significantly attenuated PMN-induced post-I/R cardiac contractile dysfunction in the isolated perfused rat heart, probably via enhanced release of endothelium-derived NO.
American Journal of Physiology - Heart and Circulatory Physiology
Young, Lindon; Ikeda, Yasuhiko; and Lefer, Allan M., "Caveolin-1 peptide exerts cardioprotective effects in myocardial ischemia-reperfusion via nitric oxide mechanism" (2001). PCOM Scholarly Papers. 465.