Abstract
BackgroundHeart failure(HF) is a dangerous disease that affects millions of patients. Radix Salvia is widely used in Chinese clinics to treat heart diseases. Salvianolic acid B(SalB) is the major active component of Radix Salvia. This study investigated the mechanisms of action and effects of SalB on HF in an experimental mouse model of HF.MethodsWe created a mouse model of HF by inducing pressure overload with transverse aortic constriction(TAC) surgery for 2 weeks and compared among 4 study groups: SHAM group (n = 10), TAC group (n = 9), TAC+MET group (metprolol, positive drug treatment, n = 9) and TAC+SalB group (SalB, 240 mg•kg-1•day-1, n = 9). Echocardiography was used to evaluate the dynamic changes in cardiac structure and function in vivo. Plasma brain natriuretic peptide (BNP) concentration was detected by Elisa method. In addition, H9C2 rat cardiomyocytes were cultured and Western blot were implemented to evaluate the phosphorylation of ERK1/2, AKT, and protein expression of GATA4.ResultsSalB significantly inhibited the phosphorylation of Thr202/Tyr204 sites of ERK1/2, but not Ser473 site of AKT, subsequently inhibited protein expression of GATA4 and plasma BNP(P < 0.001), and then inhibited HF at 2 weeks after TAC surgery.ConclusionsOur data provide a mechanism of inactivating the ERK1/2/GATA4 signaling pathway for SalB inhibition of the TAC-induced HF.
Highlights
Heart failure(HF) affects more than 37.7 million patients in the world [1]
aortic pressure gradient (AoPg) were much higher in transverse aortic constriction (TAC), TAC+ MET, and TAC+Salvianolic acid B (SalB) groups compared with SHAM group(Fig 2B, TAC, 65.56 ± 4.07 mmHg; TAC+MET, 67.12 ± 0.68 mmHg; TAC+SalB, 63.26 ± 2.19 mmHg; SHAM, 3.029 ± 0.40 mmHg, P 0.05)
In order to explore whether SalB has any independent effects on heart function or myocardial injury, we compared the SHAM + SalB with SHAM group using both mice and rat animals, there were no significant differences in heart function(EF,fractional shortening (FS), the ratio of LW/tibial length (TL), Lung/ TL, and Liver/TL), structural changes(LVPWd, inner dimension of diastolic LV (LVIDd), heart weight (HW) and LV weight (LVW)), and myocardial injury between the SHAM + SalB and SHAM groups
Summary
Heart failure(HF) affects more than 37.7 million patients in the world [1]. 17.3 million people died from heart diseases in 2013, which represents a 41% increase from 1990 [2]. The increase in heart diseases burden is mainly due to ageing population and HF [3]. Patients with HF are commonly treated with pharmacological therapies to control the symptoms, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, betablockers, and mineralocorticoid receptor antagonist, etc. Heart failure(HF) is a dangerous disease that affects millions of patients. Radix Salvia is widely used in Chinese clinics to treat heart diseases. Salvianolic acid B(SalB) is the major active component of Radix Salvia.
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