Gongchang Guan

Telmisartan delays myocardial fibrosis in rats with hypertensive left ventricular hypertrophy by TGF-β1/Smad signal pathway

Hypertensive myocardial remodeling has an important role in the pathophysiology of hypertensive disease. This study suggests that telmisartan (TEL) can inhibit myocardial fibrosis of hypertensive left ventricular hypertrophy (LVH) through the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. Through echocardiography and hemodynamics, it was shown that TEL could improve cardiac function and reduce the degree of hypertensive LVH in hypertensive rats. Through immunoassay, it was shown that TEL could antagonize renin–angiotensin–aldosterone system expression in plasma and myocardial tissue. By Masson staining, Elisa and alkaline hydrolysis assays, it was demonstrated that TEL could significantly inhibit myocardial fibrosis in hypertensive rats and attenuate extracellular matrix-related proteins associated with pressure overload. Western blotting was used to detect the TGF-β1/Smad signaling pathway protein expression of myocardial tissue, and it was further found that TEL could inhibit activation of the TGF-β1/Smad signaling pathway. In conclusion, TEL could inhibit myocardial local angiotensin II (Ang II) level by directly affecting the Ang II receptor. TEL may also restore the balance of matrix metalloproteinases/tissue inhibitor of metalloproteinases, reduce myocardial collagen fibrosis and delay hypertensive LVH by affecting the TGF-β1/Smad signaling pathway.

Matrine suppresses cardiac fibrosis by inhibiting the TGF‑β/Smad pathway in experimental diabetic cardiomyopathy

Cardiac fibrosis is one of the pathological characteristics of diabetic cardiomyopathy (DbCM). Matrine treatment has proven to be effective in cases of organ fibrosis and cardiovascular diseases. In the present study, the anti-fibrosis-associated cardioprotective effects of matrine on DbCM were investigated. Rats with experimental DbCM were administered matrine orally. Cardiac functions were evaluated using invasive hemodynamic examinations. Cardiac compliance was assessed in isolated hearts. Using Sirius Red and fluorescence staining, the collagen in diabetic hearts was visualized. MTT assay was used to select non-cytotoxic concentrations of matrine, which were subsequently used to treat isolated cardiac fibroblasts incubated under various conditions. Western blotting was performed to assess activation of the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. Rats with DbCM exhibited impaired heart compliance and left ventricular (LV) functions. Excessive collagen deposition in cardiac tissue was also observed. Furthermore, TGF-β1/R-Smad (Smad2/3) signaling was revealed to be markedly activated; however, the expression of inhibitory Smad (I-Smad, also termed Smad7) was reduced in DbCM. Matrine administration led to a marked recovery in LV function and heart compliance by exerting inhibitory effects on TGF-β1/R-Smad signaling pathway-induced fibrosis without affecting I-Smad. Incubation with a high concentration of glucose triggered the TGF-β1/R-Smad (Smad2/3) signaling pathway and suppressed I-Smad signaling transduction in cultured cardiac fibroblasts, which led to an increase in the synthesis of collagen. After cardiac fibroblasts had been treated with matrine at non-cytotoxic concentrations without affecting I-Smad, matrine blocked TGF-β1/R-Smad signaling transduction to repress collagen production and deposition. In conclusion, the results of the present study demonstrated that TGF-β1/Smad signaling-associated cardiac fibrosis is involved in the impairment of heart compliance and LV dysfunction in DbCM. By exerting therapeutic effects against cardiac fibrosis via its influence on TGF-β1/Smad signaling, matrine exhibited cardioprotective effects in DbCM.

Elevation of Fasting Ghrelin in Healthy Human Subjects Consuming a High-Salt Diet: A Novel Mechanism of Obesity?

Overweight/obesity is a chronic disease that carries an increased risk of hypertension, diabetes mellitus, and premature death. Several epidemiological studies have demonstrated a clear relationship between salt intake and obesity, but the pathophysiologic mechanisms remain unknown. We hypothesized that ghrelin, which regulates appetite, food intake, and fat deposition, becomes elevated when one consumes a high-salt diet, contributing to the progression of obesity. We, therefore, investigated fasting ghrelin concentrations during a high-salt diet. Thirty-eight non-obese and normotensive subjects (aged 25 to 50 years) were selected from a rural community in Northern China. They were sequentially maintained on a normal diet for three days at baseline, a low-salt diet for seven days (3 g/day, NaCl), then a high-salt diet for seven days (18 g/day). The concentration of plasma ghrelin was measured using an immunoenzyme method (ELISA). High-salt intake significantly increased fasting ghrelin levels, which were higher during the high-salt diet (320.7 ± 30.6 pg/mL) than during the low-salt diet (172.9 ± 8.9 pg/mL). The comparison of ghrelin levels between the different salt diets was statistically-significantly different (p < 0.01). A positive correlation between 24-h urinary sodium excretion and fasting ghrelin levels was demonstrated. Our data indicate that a high-salt diet elevates fasting ghrelin in healthy human subjects, which may be a novel underlying mechanism of obesity.