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- W3203710843 abstract "Until recently, carbon monoxide (CO) was thought of a toxic gaseous waste product of heme catabolism. Although recent evidence following left anterior descending artery (LAD) ligation in rats has suggested a potential cardioprotective effect of low dose inhaled CO, the molecular mechanism underlying this protection are obscure. The purpose of this study was to elucidate the mechanistic basis for this effect. Myocardial ischemia-reperfusion injury (LAD ligation) was performed in mice which were exposed to room air (RA) or low dose CO (250 ppm) 24 hrs before ischemia. Myocardial infarct size was significantly diminished (by 38%; p<0.01, n=6) in the CO group compared with the RA group. As one pathway of ischemic preconditioning is believed to be mediated by cycloxygenase (COX)-2, we hypothesized that CO might upregulate COX-2 to elicit ischemic cardioprotection. CO increased COX-2 expression in the hearts of mice in a time-dependent manner, peaking at 24 hrs with 4.8-fold protein induction. Additional experiments, done to test a potential separate mechanism of ischemic cardioprotection by CO, showed that CO increased HIF-1α 5.2 fold. The expression of HIF-1α and COX-2 were also higher in CO-exposed cardiomyocytes (HL-1 cells) compared with RA-exposed HL-1 cells. Treatment of HL-1 cells with the COX-2 specific inhibitor (NS398) and prostaglandin (PGE2) had no effect on HIF-1α mRNA levels. However, NS398 significantly abrogated (by 62%, p<0.05, n=3) the increase of HIF-1α expression induced by CO, and PGE2 significantly increased (by 34%, P<0.05, n=3) the HIF-1α expression of RA-exposed inhaled HL-1 cells. Moreover, treatment of mice with NS398 almost completely abolished the cardioprotective effect of CO against ischemia-reperfusion injury. This finding suggests that CO stabilizes HIF-1α via COX-2 activation of prostaglandin E2 synthesis in the heart, and implies that CO protects the heart in ischemia-reperfusion injury via stabilization of HIF-1α." @default.
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- W3203710843 date "2008-10-28" @default.
- W3203710843 modified "2023-09-25" @default.
- W3203710843 title "Abstract 364: Cardioprotective Effects Of Carbon Monoxide Mediated By Hypoxia-inducible Factor (HIF) 1-alpha" @default.
- W3203710843 doi "https://doi.org/10.1161/circ.118.suppl_18.s_291-b" @default.
- W3203710843 hasPublicationYear "2008" @default.
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