Tongxinluo Protects against Pressure Overload–Induced Heart Failure in Mice Involving VEGF/Akt/eNOS Pathway Activation

• DOI: 10.1371/journal.pone.0098047
• Publication Date: 2014-06-02T22:19:59Z
• Authors: Bo Wang; Qing Yang; Wen-wu Bai; Yi-fan Xing; Xiao-ting Lu; Yuan-yuan Sun; Yu-xia Zhao
• Keywords: Pressure overload; NOX4

Background It 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 nitric oxide synthase (eNOS). The present study aimed to investigate whether TXL protects against pressure overload–induced failure mice explore the possible mechanism of action. Methods Results Transverse aortic constriction (TAC) surgery was performed induce failure. Cardiac function evaluated by echocardiography. Myocardial pathology detected using hematoxylin eosin or Masson trichrome staining. We investigated cardiomyocyte ultrastructure transmission electron microscopy. Angiogenesis oxidative stress levels were determined CD31 8-hydroxydeoxyguanosine immunostaining malondialdehyde assay, respectively. Fetal gene expression measured real-time PCR. Protein VEGF, phosphorylated (p)-VEGF receptor 2 (VEGFR2), p–phosphatidylinositol 3-kinase (PI3K), p-Akt, p-eNOS, heme oxygenase-1 (HO-1), NADPH oxidase 4 (Nox4) with western blotting. Twelve-week low- high-dose treatment following TAC improved cardiac systolic diastolic ameliorated left ventricular hypertrophy, fibrosis, myocardial derangement. Importantly, increased capillary density significantly attenuated injury failing hearts. Moreover, upregulated nitrite content protein p-VEGFR2, p-PI3K, HO-1, but decreased Nox4 mouse TAC. Conclusion Our findings indicate mice. Activation VEGF/Akt/eNOS signaling pathway might be involved improvement heart.