Hydroxysafflor yellow A mitigates myocardial fibrosis induced by isoproterenol and angiotensin II.

AIMS: To investigate the potential inhibitory effect of Hydroxysafflor yellow A (HSYA) on myocardial fibrosis induced by isoproterenol (ISO) and angiotensin II (Ang II) and the possible underlying mechanism. METHODS: Mice were injected subcutaneously with ISO and given HSYA by gavage in vivo. Masson's trichrome staining, immunohistochemical staining and immunofluorescence assays were conducted to evaluate the expression and localization of collagen and inflammatory cytokines, respectively. In vitro, cardiac fibroblasts (CFs) were treated with various doses of HSYA and induced with Ang II. Cell proliferation and migration were assessed using wound healing assay. Cell counting kit-8 was used to measure the cell viability. Collagen I, collagen III, phosphorylation of Smad2/3, Smad2/3, TGFß1, interleukin (IL)-1ß, IL-18, NLRP3 inflammasome-associated proteins were detected by Western blotting. Levels of reactive oxygen species (ROS) were evaluated using 2',7'-dichlorofluorescein diacetate assay. RESULTS: HSYA significantly inhibited ISO-induced myocardial fibrosis, NLRP3 inflammasome activation as well as IL-18 and IL-1ß expressions in mice. HSYA significantly reduced the proliferation and migration of CFs, and suppressed the accumulation of collagen I and collagen III. TGFß1 and P-Smad2/3 induced by Ang II was repressed by HSYA. HSYA downregulated IL-1ß and IL-18, blocked NLRP3 activation, and reduced ROS in CFs. CONCLUSION: HSYA may inhibit myocardial fibrosis by blocking NLRP3 pathway in CFs.

Telmisartan suppresses cardiac hypertrophy by inhibiting cardiomyocyte apoptosis via the NFAT/ANP/BNP signaling pathway.

Telmisartan, a type of angiotensin II (Ang II) receptor inhibitor, is a common agent used to treat hypertension in the clinic. Hypertension increases cardiac afterload and promotes cardiac hypertrophy. However, the ventricular Ang II receptor may be activated in the absence of hypertension. Therefore, telmisartan may reduce cardiac hypertrophy by indirectly ameliorating hypertensive symptoms and directly inhibiting the cardiac Ang II receptor. Nuclear factor of activated T­cells (NFAT) contributes to cardiac hypertrophy via nuclear translocation, which induces a cascade of atrial natriuretic peptide (ANP) and brain/B­type natriuretic peptide (BNP) expression and cardiomyocyte apoptosis. However, NFAT-mediated inhibition of cardiac hypertrophy by telmisartan remains poorly understood. The present study demonstrated that telmisartan suppressed cardiomyocyte hypertrophy in a mouse model of cardiac afterload and in cultured cardiomyocytes by inhibiting NFAT nuclear translocation, as well as by inhibiting ANP and BNP expression and cardiomyocyte apoptosis, in a dose­dependent manner. The present study provides a novel insight into the potential underlying mechanisms of telmisartan-induced inhibition of cardiomyocyte hypertrophy, which involves inhibition of NFAT activation, nuclear translocation and the ANP/BNP cascade.