Abstract
BackgroundOxidative stress is an important factor involved in the progress of heart failure. The current study was performed to investigate whether pinocembrin was able to ameliorate post-infarct heart failure (PIHF) and the underlying mechanisms.MethodsRats were carried out left anterior descending artery ligation to induce myocardial infarction and subsequently raised for 6 weeks to produce chronic heart failure. Then pinocembrin was administrated every other day for 2 weeks. The effects were evaluated by echocardiography, western blot, Masson’s staining, biochemical examinations, immunohistochemistry, and fluorescence. In vitro we also cultured H9c2 cardiomyocytes and cardiac myofibroblasts to further testify the mechanisms.ResultsWe found that PIHF-induced deteriorations of cardiac functions were significantly ameliorated by administrating pinocembrin. In addition, the pinocembrin treatment also attenuated collagen deposition and augmented vascular endothelial growth factor receptor 2 in infarct border zone along with an attenuated apoptosis, which were related to an amelioration of oxidative stress evidenced by reduction of reactive oxygen species (ROS) in heart tissue and malondialdehyde (MDA) in serum, and increase of superoxide dismutase (SOD). This were accompanied by upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) pathway. In vitro experiments we found that specific Nrf2 inhibitor significantly reversed the effects resulted from pinocembrin including antioxidant, anti-apoptosis, anti-fibrosis and neovascularization, which further indicated the amelioration of PIHF by pinocembrin was in a Nrf2/HO-1 pathway-dependent manner.ConclusionPinocembrin ameliorated cardiac functions and remodeling resulted from PIHF by ROS scavenging and Nrf2/HO-1 pathway activation which further attenuated collagen fibers deposition and apoptosis, and facilitated angiogenesis.
Highlights
Heart failure (HF), characterized by a range of terminal clinical syndromes resulted from structural and/ or functional impairments of heart, remains a global healthy burden, with myocardial infarction (MI) as the leading cause (Ziaeian and Fonarow 2016; Galli and Lombardi 2016; Rengo et al 2013)
Pino ameliorated HF‐induced deterioration of cardiac functions We firstly implemented echocardiography to determine the HF phenotype establishment induced by left anterior descending coronary artery (LAD) ligation and the effects exerted by Pino on cardiac functions
To avoid the artificial bias in the infarct border zone judgement, we established identical model as positive control, in which Pino was replaced by enalapril, an angiotensin-converting enzyme inhibitor (ACEI) known for the reversal on HF remodeling
Summary
Heart failure (HF), characterized by a range of terminal clinical syndromes resulted from structural and/ or functional impairments of heart, remains a global healthy burden, with myocardial infarction (MI) as the leading cause (Ziaeian and Fonarow 2016; Galli and Lombardi 2016; Rengo et al 2013). The current dilemma might ascribe partly to that post-infarct HF (PIHF) consists of a wide variety of pathophysiological mechanisms to which present therapeutic methods are not able to completely refer. Accumulating studies have shown that oxidative stress (OS) is predominantly involved in the pathological progression of PIHF (Dubois-Deruy et al 2020; Ma et al 2019; Bubb et al 2017; Habtemariam 2019). Oxidative stress is an important factor involved in the progress of heart failure. The current study was performed to investigate whether pinocembrin was able to ameliorate post-infarct heart failure (PIHF) and the underlying mechanisms
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