Abstract
The present study aimed to determine whether apelin-13 could attenuate cardiac fibrosis via inhibiting the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway to inhibit reactive oxygen species in heart failure (HF) rats. HF models were established by inducing ischemia myocardial infarction (MI) through ligation of the left anterior descending artery in Sprague–Dawley (SD) rats. MI-induced changes in hemodynamics and cardiac function were reversed by apelin-13 administration. The increases in the levels of collagen I, collagen III, α-smooth muscle actin (SMA), and transforming growth factor-β (TGF-β) in the heart of MI rats and cardiac fibroblasts (CFs) treated with angiotensin (Ang) II were inhibited by apelin-13. The levels of PI3K and p-Akt increased in Ang II-treated CFs, and these increases were blocked by apelin-13. The PI3K overexpression reversed the effects of apelin-13 on Ang II-induced increases in collagen I, collagen III, α-SMA, and TGF-β, NADPH oxidase activity and superoxide anions in CFs. Apelin-13 reduced the increases in the levels of NADPH oxidase activity and superoxide anions in the heart of MI rats and CFs with Ang II treatment. The results demonstrated that apelin-13 improved cardiac dysfunction, impaired cardiac hemodynamics, and attenuated fibrosis of CFs induced by Ang II via inhibiting the PI3K/Akt signaling pathway to inhibit oxidative stress.
Highlights
Chronic heart failure (CHF) is commonly caused by myocardial infarction (MI) [1]
LV end-diastolic pressure (LVEDP), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), LV volumes in systole (LVVs), and left ventricular volume in diastole (LVVd) increased in rats with MI, which were reversed by apelin-13 treatment (Figure 2)
The protein levels of collagen I, collagen III, and transforming growth factor (TGF)-β increased in the heart of MI rats, and apelin-13 treatment attenuated the increases in the protein levels of collagen I, collagen III, and transforming growth factor-β (TGF-β) in the heart of MI rats (Figure 3C)
Summary
Chronic heart failure (CHF) is commonly caused by myocardial infarction (MI) [1]. Heart failure (HF) is preceded by ventricular remodelings such as changes in left ventricular (LV) mass and myocardial size after alterations in pressure-overload conditions [2]. Cardiac fibrosis is a major driver of disease progression in CHF [4], and excessive fibrosis causes large infarct scars, resulting in cardiac dilatation and cardiac dysfunction [5,6]. Resident cardiac fibroblasts (CFs) are currently considered as the main source of fibrosis in the myocardium in response to ischemic injury [7]. CFs played a critical role in postinfarction remodeling, which can lead to pathological fibrosis and HF [8]. Cardiac fibrosis is a hallmark of HF for which no effective pharmacological therapy is available
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