Abstract
BackgroundIt has been demonstrated that Tongxinluo (TXL), a traditional Chinese medicine compound, improves ischemic heart disease in animal models via vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). The present study aimed to investigate whether TXL protects against pressure overload–induced heart failure in mice and explore the possible mechanism of action.Methods and ResultsTransverse aortic constriction (TAC) surgery was performed in mice to induce heart failure. Cardiac function was evaluated by echocardiography. Myocardial pathology was detected using hematoxylin and eosin or Masson trichrome staining. We investigated cardiomyocyte ultrastructure using transmission electron microscopy. Angiogenesis and oxidative stress levels were determined using CD31 and 8-hydroxydeoxyguanosine immunostaining and malondialdehyde assay, respectively. Fetal gene expression was measured using real-time PCR. Protein expression of VEGF, phosphorylated (p)-VEGF receptor 2 (VEGFR2), p–phosphatidylinositol 3-kinase (PI3K), p-Akt, p-eNOS, heme oxygenase-1 (HO-1), and NADPH oxidase 4 (Nox4) were measured with western blotting. Twelve-week low- and high-dose TXL treatment following TAC improved cardiac systolic and diastolic function and ameliorated left ventricular hypertrophy, fibrosis, and myocardial ultrastructure derangement. Importantly, TXL increased myocardial capillary density significantly and attenuated oxidative stress injury in failing hearts. Moreover, TXL upregulated cardiac nitrite content and the protein expression of VEGF, p-VEGFR2, p-PI3K, p-Akt, p-eNOS, and HO-1, but decreased Nox4 expression in mouse heart following TAC.ConclusionOur findings indicate that TXL protects against pressure overload–induced heart failure in mice. Activation of the VEGF/Akt/eNOS signaling pathway might be involved in TXL improvement of the failing heart.
Highlights
Heart failure is a major cause of mortality worldwide
Our findings indicate that TXL protects against pressure overload–induced heart failure in mice
A common cause of heart failure is chronic pressure overload due to hypertension or aortic stenosis, which leads to cardiac hypertrophy that may progress to heart failure [1]
Summary
A common cause of heart failure is chronic pressure overload due to hypertension or aortic stenosis, which leads to cardiac hypertrophy that may progress to heart failure [1]. The mechanism mediating the pathological changes responsible for heart failure has not been fully elucidated, experimental evidence suggests that disruption of coordinated tissue growth and angiogenesis may contribute to the development of pressure overload–induced cardiac hypertrophy and heart failure [2,3]. Gene therapy of VEGF overexpression ameliorates angiotensin II–induced diastolic dysfunction by promoting angiogenesis and anti-inflammation function [3]. The present study aimed to investigate whether TXL protects against pressure overload–induced heart failure in mice and explore the possible mechanism of action
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