Hydrogen sulfide suppresses the expression of MMP-8, MMP-13, and TIMP-1 in left ventricles of rats with cardiac volume overload

• Published in: Acta pharmacologica Sinica Vol. 34; no. 10; pp. 1301 - 1309
• Main Authors: Zhang, Chao-ying, Li, Xiao-hui, Zhang, Ting, Fu, Jin, Cui, Xiao-dai
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2013; Nature Publishing Group
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Blotting, Western; Cardiac Volume; Disease Models, Animal; Gene Expression Regulation; Heart Defects, Congenital - physiopathology; Heart Ventricles - metabolism; Heart Ventricles - physiopathology; Hydrogen Sulfide - metabolism; Immunology; Internal Medicine; Male; Matrix Metalloproteinase 13 - genetics; Matrix Metalloproteinase 8 - genetics; Medical Microbiology; mRNA表达水平; Original; original-article; Pharmacology/Toxicology; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; RNA, Messenger - metabolism; Sulfides - pharmacology; TIMP-1; Tissue Inhibitor of Metalloproteinase-1 - genetics; Vaccine; Ventricular Remodeling; 大鼠模型; 容量; 左心室; 心脏疾病; 硫化氢; 超负荷; hydrogen sulfide; collagen I; congenital heart disease; MMP-13; ventricular remodeling; MMP-8; tissue inhibitor of metalloproteinase 1; cardiac volume overload; hydroxyproline
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2013.84

Aim： To study the effects of hydrogen sulfide （H2S） on the left ventricular expression of MMP-8, MMP-13, and TIMP-1 in a rat model of congenital heart disease. Methods： Male SD rats underwent abdominal aorta-inferior vena cava shunt operation. H2S donor NariS （56 μmol.kg-1.d-1, ip） was injected from the next day for 8 weeks. At 8 weeks, the hemodynamic parameters, including the left ventricular systolic pressure （LVSP）, the left ventricular peak rate of contraction and relaxation （LV＋dp/dtmax） and the left ventricular end diastolic pressure （LVEDP） were measured. The left ventricular tissues were dissected out, and hydroxyproline and collagen I contents were detected with ELISA. The expression of MMP-8, MMP-13, and a tissue inhibitor of metalloproteinase-1 （TIMP-1） in the tissues was measured using real-time PCR, Western blotting, and immunohistochemistry, respectively. Results： The shunt operation markedly reduced LVSP and LV＋dp/dtmax, increased LVEDP, hydroxyproline and collagen I contents, as well as the mRNA and protein levels of MMP-8, MMP-13, and TIMP-1 in the left ventricles. Chronic treatment of the shunt operation rats with NariS effectively prevented the abnormalities in the hemodynamic parameters, hydroxyproline and collagen I contents, and the mRNA and protein levels of MMP-13 and TIMP-1 in the left ventricles. NariS also prevented the increase of MMP-8 protein expres- sion, but did not affect the increase of mRNA level of MMP-8 in the shunt operation rats. Conclusion： H2S suppresses protein and mRNA expression of MMP-8, MMP-13, and TIMP-1 in rats with cardiac volume overload, which may be contributed to the amelioration of ventricular structural remodeling and cardiac function.