Int J Biol Sci 2012; 8(4):430-441. doi:10.7150/ijbs.3632
Hydrogen Sulfide Mitigates Cardiac Remodeling During Myocardial Infarction via Improvement of Angiogenesis
Departments of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky- 40202.
Exogenous hydrogen sulfide (H2S) leads to down-regulation of inflammatory responses and provides myocardial protection during acute ischemia/reperfusion injury; however its role during chronic heart failure (CHF) due to myocardial infarction (MI) is yet to be unveiled. We previously reported that H2S inhibits antiangiogenic factors such, as endostatin and angiostatin, but a little is known about its effect on parstatin (a fragment of proteinase-activated receptor-1, PAR-1). We hypothesize that H2S inhibits parstatin formation and promotes VEGF activation, thus promoting angiogenesis and significantly limiting the extent of MI injury. To verify this hypothesis MI was created in 12 week-old male mice by ligation of left anterior descending artery (LAD). Sham surgery was performed except LAD ligation. After the surgery mice were treated with sodium hydrogen sulfide (30 μmol/l NaHS, a donor for H2S, in drinking water) for 4 weeks. The LV tissue was analyzed for VEGF, flk-1 and flt-1, endostatin, angiostatin and parstatin. The expression of VEGF, flk-1 and flt-1 were significantly increased in treated mice while the level of endostatin, angiostatin and parstatin were decreased compared to in untreated mice. The echocardiography in mice treated with H2S showed the improvement of heart function compared to in untreated mice. The X-ray and Doppler blood flow measurements showed enhancement of cardiac-angiogenesis in mice treated with H2S. This observed cytoprotection was associated with an inhibition of anti-angiogenic proteins and stimulation of angiogenic factors. We established that administration of H2S at the time of MI ameliorated infarct size and preserved LV function during development of MI in mice. These results suggest that H2S is cytoprotective and angioprotective during evolution of MI.
Keywords: Hydrogen sulfide, VEGF, flk-1, flt-1, endostatin, angiostatin, parstatin Myocardial infarction
Qipshidze N, Metreveli N, Mishra PK, Lominadze D, Tyagi SC. Hydrogen Sulfide Mitigates Cardiac Remodeling During Myocardial Infarction via Improvement of Angiogenesis. Int J Biol Sci 2012; 8(4):430-441. doi:10.7150/ijbs.3632. Available from http://www.ijbs.com/v08p0430.htm