[Show abstract][Hide abstract] ABSTRACT: 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.
Male SD rats underwent abdominal aorta-inferior vena cava shunt operation. H2S donor NaHS (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.
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 NaHS 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. NaHS also prevented the increase of MMP-8 protein expression, but did not affect the increase of mRNA level of MMP-8 in the shunt operation rats.
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.
Preview · Article · Aug 2013 · Acta Pharmacologica Sinica
[Show abstract][Hide abstract] ABSTRACT: The present study investigated the role of hydrogen sulfide (H2S), a novel gaseous transmitter, in chronic heart failure (CHF) induced by left-to-right shunt, leading to volume overload. Thirty male Sprague-Dawley rats were randomly divided into four groups: the shunt group, the sham group, the shunt + sodium hydrosulfide (NaHS) group and the sham + NaHS group. CHF was induced in the rats by abdominal aorta-inferior vena cava shunt operation. Rats in the shunt + NaHS and sham + NaHS groups were injected intraperitoneally with NaHS (H2S donor). Haemodynamic parameters were measured 8 weeks after surgery. In addition, left ventricular heme oxygenase (HO)-1 mRNA expression was measured by real-time PCR. Protein expression of HO-1 was evaluated by western blot analysis. Eight weeks after surgery, compared to the sham group, the left ventricular systolic pressure (LVSP) and left ventricular peak rate of contraction and relaxation (LV±dp/dtmax) were significantly reduced; the left ventricular end-diastolic pressure (LVEDP) was significantly increased in the shunt group (all P<0.05). However, NaHS increased LVSP and LV±dp/dtmax (all P<0.05) and decreased LVEDP (P<0.05). Protein expression of HO-1 was significantly decreased in the shunt group compared to that in the sham group (P<0.05). NaHS increased protein expression of HO-1 compared to that in the shunt group (P<0.05). HO-1 mRNA expression was significantly increased in the shunt + NaHS group compared to that in the shunt group (P<0.01). The present study demonstrated that H2S may play a protective role in volume overload-induced CHF by upregulating protein and mRNA expression of HO-1.
[Show abstract][Hide abstract] ABSTRACT: To explore the effects of sodium hydrosulfide (NaHS), a hydrogen sulphide (H(2)S) donor, on cardiac functions and structures in rats with chronic heart failure induced by volume overload and examine its influence on cardiac remodelling.
A total of 47 SD rats (120 - 140 g) were randomly divided into 5 groups:shunt group (n = 11), sham group (n = 8), shunt + NaHS group (n = 10), sham + NaHS group (n = 8) and shunt + phentolamine group (n = 10). The rat model of chronic heart failure was induced by abdominal aorta-inferior vena cava puncture. At Week 8 post-operation, hemodynamic parameters, microstructures and ultrastructures of myocardial tissues were analyzed. Extracellular collagen content in myocardial tissues was analyzed after Sirius red staining. Right ventricular hydroxyproline concentration was determined and compared.
At Week 8 post-operation, compared with the sham operation and shunt + NaHS groups, the shunt group showed significantly increased right ventricular systolic pressure (RVSP) and right ventricular end diastolic pressure (RVEDP) (mm Hg: 35.2 ± 3.9 vs 21.4 ± 3.7 and 28.1 ± 2.7, 32 ± 5 vs 21 ± 4 and 26 ± 4, all P < 0.05, 1 mm Hg = 0.133 kPa). The RV peak rate of contraction and relaxation markedly decreased (RV ± dp/dt max) (mm Hg/s: 1528 ± 113 vs 2336 ± 185 and 1835 ± 132, 1331 ± 107 vs 2213 ± 212 and 1768 ± 116, all P < 0.05). It was found microscopically that myocardial fibers in the shunt group were irregularly arranged, partially cytolysis and infiltrated by inflammatory cells. Electron microscopy revealed that myocardial fibers thickened non-uniformly in the shunt group, some fiber mitochondria were highly swollen and contained vacuoles. And sarcoplasmic reticulum appeared slightly dilated. Polarized microscopy indicated that, collagen content (particularly type-I collagen) increased in the shunt group compared with the sham operation group. Additionally, compared with the shunt group, the shunt and NaHS treatment groups showed an amelioration of myocardial damage, an alleviation of myocardial fiber changes and a decrease in myocardial collagen content (particularly type-I collagen). Compared with the sham operation and shunt + NaHS groups, the shunt group displayed increased right ventricular hydroxyproline (mg×g(-1)·pro: 1.32 ± 0.25 vs 0.89 ± 0.18 and 0.83 ± 0.19, all P < 0.05).
H(2)S may improve cardiac functions and ameliorate cardiac structures in rats with chronic heart failure probably through dilating the blood vessels and affecting the extracellular collagen metabolism.
No preview · Article · Nov 2011 · Zhonghua yi xue za zhi
[Show abstract][Hide abstract] ABSTRACT: Cardiac involvement is the most common complication of Kawasaki disease (KD); however, the underlying mechanisms are not understood. The present study was designed to investigate changes in plasma hydrogen sulfide (H(2)S) and nitric oxide (NO) levels in the acute and recovery stages of KD children and to examine their clinical significance.
Thirty-five KD patients and 32 healthy children were enrolled in the study. KD patients were divided into two subgroups: a non-cardiac involvement group and a cardiac involvement group. Plasma H(2)S levels were measured using the sulfur-sensitive electrode method and plasma NO levels and NO synthase activity were determined using the nitrate reductase method both before and after intravenous immune globulin (IVIG) therapy.
Plasma H(2)S levels significantly decreased in KD patients during the acute phase of the disease and NO levels were significantly increased, compared with the control group (P < 0.01). After treatment with IVIG, both plasma H(2)S and NO levels significantly increased (P < 0.01). The plasma levels of H(2)S were significantly lower in the cardiac involvement group compared with the non-cardiac involvement group (P < 0.05).
H(2)S and NO may play a role in the pathophysiological process of inflammation during the acute phase of KD. Endogenous H(2)S may exert protective effects with respect to cardiac complications in KD.
No preview · Article · Nov 2011 · Chinese medical journal