Qiliqiangxin Inhibits the Development of Cardiac Hypertrophy, Remodeling, and Dysfunction During 4 Weeks of Pressure Overload in Mice

Abstract

Qiliqiangxin (QL), a traditional Chinese medicine, has been used in the treatment of chronic heart failure. However, whether QL can benefit cardiac remodeling in the hypertensive state is unknown. We here examined the effects of QL on the development of cardiac hypertrophy through comparing those of losartan in C57BL/6 mice underlying transverse aorta constriction for 4 weeks. QL and losartan were administrated at 0.6 mg and 13.4 mg·kg·d, respectively. Cardiac hypertrophy, function, and remodeling were evaluated by echocardiography, catheterization, histology, and examination of specific gene expression and ERK phosphorylation. Cardiac apoptosis, autophagy, tumor necrosis factor α/insulin-like growth factor-1, and angiotensin II type 1 receptor expression and especially the proliferation of cardiomyocytes and phosphorylation of ErbB receptors were examined in vivo to elucidate the mechanisms. Transverse aorta constriction for 2 weeks resulted in a significant cardiac hypertrophy, which was significantly suppressed by either QL or losartan treatment. At 4 weeks after transverse aorta constriction, although the development of cardiac dysfunction and remodeling and the increases in apoptosis, autophagy, tumor necrosis factor α/insulin-like growth factor-1, and angiotensin II type 1 receptor expression were abrogated comparably between QL and losartan treatments, QL, but not losartan, enhanced proliferation of cardiomyocytes, which was paralleled with dowregulation of CCAAT/enhancer-binding protein β, upregulation of CBP/p300-interacting transactivator with ED-rich carboxy-terminal domain 4, and increases in ErbB2 and ErbB4 phosphorylation. Furthermore, inhibition of either ErbB2 or CBP/p300-interacting transactivator with ED-rich carboxy-terminal domain 4 abolished the cardiac protective effects of QL. Thus, QL inhibits myocardial inflammation and cardiomyocyte death and promotes cardiomyocyte proliferation, leading to an ameliorated cardiac remodeling and function in a mouse model of pressure overload. The possible mechanisms may involve inhibition of angiotensin II type 1 receptor and activation of ErbB receptors.

Losartan treatment attenuates tumor-induced myocardial dysfunction

“…Statistical analyses indicated effects of tumor cell injection on TPS90 (p<.0001) and TR90 (p<0.05), and effects of Losartan treatment on TPS90 (p<.001) and TR90 (p<0.05). These data suggest that the effects of Losartan treatment on peak shortening and relengthening were independent of the tumor condition and could be related to the tendency of Losartan to cause hypertrophy [27, 28]. …”

Qiliqiangxin Attenuates Cardiac Remodeling via Inhibition of TGF-β1/Smad3 and NF-κB Signaling Pathways in a Rat Model of Myocardial Infarction

“…Our laboratory and others have reported that QL can attenuate myocardial remodeling and improve cardiac function in rats with experimental myocardial infarction [20-22]. Several studies have mentioned the protective effect of QL on cardiac remodeling, which are associated with inflammation regulation, energy metabolism improvement, and angiogenesis enhancement [23-26], but its mechanism has not been thoroughly elucidated to date. Therefore, using a post-myocardial infarction heart failure model, the present study evaluated the influence of QL on the heart function, cardiac fibrosis, and the expression of TGF-β1, p-Smads, collagen I, TNF-α and IL-6 to further explore whether TGF-β1 and NF-κB pathways are involved in the protective effects of QL during cardiac remodeling.…”

Clinical Aspects of Aconitum Preparations

“…It also inhibited myocardial inflammation and the death of cardiomyocytes. On the other hand, it promoted cardiomyocyte proliferation, leading to improved cardiac remodeling and cardiac function [36]. Another study showed that qili-qiangxin improved both systolic and diastolic cardiac functions, and it downregulated the cardiac chymase signaling pathway and chymase-mediated angiotensin II production in hypertensive rats [37].…”