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

Abstract

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.

Histone deacetyltransferase inhibitors Trichostatin A and Mocetinostat differentially regulate MMP9, IL-18 and RECK expression, and attenuate Angiotensin II-induced cardiac fibroblast migration and proliferation

“…Further, blockade of angiotensin II type I receptor (AT 1 ), or downregulation of AT 1, has been shown to inhibit the activation of multiple pro-fibrotic pathways in heart and kidney. [19][20][21] We have previously reported that chronic infusion of Ang-II induces IL-18 and MMP9 expression in hypertrophied mouse myocardium, but suppresses RECK expression. 22 Analogous results were obtained in cultured CF.…”

Effects of telmisartan on fat distribution: a meta-analysis of randomized controlled trials

“…Fat redistribution induced by PPAR-γ agonists is characterized by the differentiation of pre-adipocytes into small fat cells in subcutaneous fat depots and apoptosis of differentiated large adipocytes in visceral fat depots54 . In animal studies, telmisartan reduced adipocyte size and protected against obesity and steatohepatitis compared to valsartan55 , furthermore, showed cardio-protective effect in rats with hypertensive left ventricular hypertrophy56 . This change in fat distribution could explain the favorable effects of telmisartan on reducing pro-inflammatory cytokines, like IL-6 and TNF-α levels, and increasing adiponectin levels.…”

A minimally invasive endovascular rabbit model for experimental induction of progressive myocardial hypertrophy

“…11,12 Because LVH is related to many forms of heart disease, experimental models of myocardial hypertrophy constitute an important field of research in cardiology because of their applicability in the study of the pathogenesis and pathophysiology of this adaptive phenomenon, as well as in the development of novel therapeutic strategies. 13,14 In the literature, most of the existing experimental models that study the effect of increased afterload on left ventricle are based on surgery techniques. Currently, to our knowledge, the available experimental models of pressure overload-induced cardiac hypertrophy include the transverse thoracic aortic banding and the suprarenal abdominal aortic constriction applied usually in small animals like mice, rats and rabbits.…”