Abstract
Heart failure (HF) has been known as a global health problem, and cardiac remodeling plays an essential role in the development of HF. We hypothesized that YQWY decoction might exert a cardioprotective effect against myocardium inflammation, fibrosis, and apoptosis via activating the interleukin-10 (IL-10)/Stat3 signaling pathway. To test this hypothesis, the HF model in rats was established by pressure overload through the minimally invasive transverse aortic constriction (MTAC). Echocardiography was performed to assess the left ventricular function of rats. Myocardial fibrosis in rats was observed by Masson and Picrosirius red staining, and the degree of myocardial apoptosis was detected via TUNEL staining. In addition, expression levels of IL-10, tumor necrosis factor-α (TNF-α), Stat3 (P-Stat3), P65 (P-P65), CD68, collagen I, TGF-β, CTGF, Bax, Bcl-2, cleaved caspase-3, and PARP in rat serum and myocardium samples were examined by ELISA, western blot, and immunohistochemistry, respectively. YQWY decoction treatment significantly improved left ventricular function in HF rats, especially in those of the high-dose group (LVEF%: 51.29 ± 5.876 vs. 66.02 ± 1.264, P < 0.01;, LVFS%: 27.75 ± 3.757 vs. 37.76 ± 1.137, P < 0.01). Furthermore, YQWY decoction markedly inhibited MTAC-induced myocardial fibrosis as evidenced by downregulated collagen I, TGF-β, and CTGF in myocardium and alleviated apoptosis (downregulated caspase-3 and PARP and increased Bcl-2/Bax ratio in cardiomyocytes). In addition, YQWY decoction decreased the level of the proinflammatory cytokine TNF-α in both circulating blood and myocardium and attenuated infiltration of inflammatory cells in heart tissue from HF rats. Most importantly, YQWY decoction suppressed MTAC-induced NF-κB activation and phosphorylated Stat3 by upregulating IL-10 in rat heart tissues. Our study showed that YQWY decoction could attenuate MTAC-induced myocardial inflammation, fibrosis, apoptosis, and reverse the impairment of cardiac function in rats by activating the IL-10/Stat3 signaling pathway and improving myocardium remodeling. Our findings suggested a therapeutic potential of YQWY decoction in HF.
Highlights
Heart failure (HF) affects more than 2% of the general population, which is a major public health concern that costs a high economic burden on the health system [1]
Cardiac fibrosis is a crucial event in the pathological process of ventricular remodeling. erefore, we assessed fibrotic changes in HF rats with Yi Qi Wen Yang (YQWY) treatment
Our results showed upregulated IL-10 and downregulated NF-κB in HF rats treated by YQWY decoction, which may be explained by the phosphorylation of signal transducer and activator of transcription 3 (Stat3)
Summary
Heart failure (HF) affects more than 2% of the general population, which is a major public health concern that costs a high economic burden on the health system [1]. Cardiac remodeling has been considered as a key factor in the progress of HF [2]. Many clinical studies have demonstrated that reversal of cardiac remodeling can alleviate the progress of HF [3, 4]. Several important signaling pathways, such as cell death signaling, calcium handling, myocardial energy metabolism, Evidence-Based Complementary and Alternative Medicine oxidative stress, and neurohormonal activation are involved in the pathophysiology of myocardial dysfunction and remodeling [5]. Some agents targeting neurohumoral activation process, such as renin-angiotensin-aldosterone system (RAAS) inhibitors and β-adrenergic receptor blockaders, have been considered as first-line treatments that are beneficial to the prognosis of HF [6, 7], morbidity and mortality of HF remain high in clinical practice
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