Hydrogen sulfide mitigates transition from compensatory hypertrophy to heart failure.

Abstract

We reported previously that although there is disruption of coordinated cardiac hypertrophy and angiogenesis in transition to heart failure, matrix metalloproteinase (MMP)-9 induced antiangiogenic factors play a vital role in this process. Previous studies have shown the cardioprotective role of hydrogen sulfide (H₂S) in various cardiac diseases, but its role during transition from compensatory hypertrophy to heart failure is yet to be unveiled. We hypothesize that H₂S induces MMP-2 activation and inhibits MMP-9 activation, thus promoting angiogenesis, and mitigates transition from compensatory cardiac hypertrophy to heart failure. To verify this, aortic banding (AB) was created to mimic pressure overload in wild-type (WT) mice, which were treated with sodium hydrosulfide (NaHS, H₂S donor) in drinking water and compared with untreated control mice. Mice were studied at 3 and 8 wk. In the NaHS-treated AB 8 wk group, the expression of MMP-2, CD31, and VEGF was increased while the expression of MMP-9, endostatin, angiostatin, and tissue inhibitor of matrix metalloproteinase (TIMP)-3 was decreased compared with untreated control mice. There was significant reduction in fibrosis in NaHS-treated groups. Echocardiograph and pressure-volume data revealed improvement of cardiac function in NaHS-treated groups over untreated controls. These results show that H₂S by inducing MMP-2 promotes VEGF synthesis and angiogenesis while it suppresses MMP-9 and TIMP-3 levels, inhibits antiangiogenic factors, reduces intracardiac fibrosis, and mitigates transition from compensatory hypertrophy to heart failure.

• Authors: Srikanth Givvimani, Charu Munjal, Riyad Gargoum, Utpal Sen, Neetu Tyagi, Jonathan C Vacek, Suresh C Tyagi
• Journal: Journal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 110 Issue 4 Pg. 1093-100 (Apr 2011) ISSN: 1522-1601 [Electronic] United States
• PMID: 21233344 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Platelet Endothelial Cell Adhesion Molecule-1
• Tissue Inhibitor of Metalloproteinase-3
• Vascular Endothelial Growth Factor A
• Matrix Metalloproteinase 2
• Hydrogen Sulfide

Topics

• Analysis of Variance
• Animals
• Blotting, Western
• Cardiomegaly (metabolism)
• Disease Progression
• Echocardiography
• Heart Failure (metabolism)
• Hydrogen Sulfide (metabolism)
• Immunohistochemistry
• Matrix Metalloproteinase 2 (metabolism)
• Mice
• Mice, Inbred C57BL
• Myocardium (metabolism)
• Platelet Endothelial Cell Adhesion Molecule-1 (metabolism)
• Tissue Inhibitor of Metalloproteinase-3 (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)