BYD Ameliorates Oxidative Stress-Induced Myocardial Apoptosis in Heart Failure Post-Acute Myocardial Infarction via the P38 MAPK-CRYAB Signaling Pathway.

Yi Zhang,Yong Wang,Qian Zhang,Qixin Wang,Pengfei Tu,Chun Li,Hui Meng,Dongqing Guo,Wenji Lu

doi:10.3389/fphys.2018.00505

Yi Zhang, Yong Wang + Show 7 more

Open Access

https://doi.org/10.3389/fphys.2018.00505

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Abstract

Aim: Heart failure (HF) post-acute myocardial infarction (AMI) contributes to increasing mortality and morbidity worldwide. Baoyuan decoction (BYD) is a well-known traditional Chinese medicine formula that exhibits myocardial protection clinically. The aim of this study was to identify the effects of BYD on oxidative stress-induced apoptosis in HF post-AMI and characterize the underlying mechanism.Methods and Results: In our study, we constructed left anterior descending (LAD)-induced AMI rat models and a macrophage-conditioned media (CM)-induced H9C2 injury model. In vivo, BYD could protect cardiac functions, decrease inflammatory cell infiltration and inhibit oxidative stress-induced apoptosis. In vitro, BYD inhibited cellular apoptosis and regulated the expressions of key apoptotic molecules, including reducing the expression of B cell lymphoma-2 (Bcl-2) associated X protein (Bax) and cleaved caspase-3 and -9. Interestingly, the P38 mitogen-activated protein kinase (MAPK)-αB-crystallin (CRYAB) signaling pathway was activated by BYD treatment, and the P38 MAPK inhibitor SB203580 could reverse the protective effects of BYD.Conclusion: This study identified that BYD protected against oxidative stress-induced myocardial apoptosis via the P38 MAPK-CRYAB pathway. CRYAB may become a novel therapeutic target for AMI.

Highlights

Acute myocardial infarction (AMI) is a severe cardiovascular disease that can lead to heart failure (HF) and malignant arrhythmia, which are responsible for increasing mortality and morbidity worldwide (Plakht et al, 2015; Sacks et al, 2015)
B cell lymphoma-2 (Bcl-2) associated X protein (Bax), caspase 3, caspase 9 related to the mitochondrial apoptotic pathway are activated, and Bcl-2, which has an antiapoptotic effect against the mitochondrial apoptotic pathway, is inhibited
left ventricular internal diameter at end-diastole (LVIDd) and left ventricular internal diameter at end-systole (LVIDs) were increased in the model group (P < 0.001), indicating that both heart dysfunction and structural change occurred

Summary

Introduction

Acute myocardial infarction (AMI) is a severe cardiovascular disease that can lead to heart failure (HF) and malignant arrhythmia, which are responsible for increasing mortality and morbidity worldwide (Plakht et al, 2015; Sacks et al, 2015). The focus has been on elucidating the underlying mechanisms and exploring new therapeutic targets for HF post-AMI. Accumulating evidence has demonstrated that oxidative stress-induced apoptosis is an attractive target for HF postAMI (Shahzad et al, 2017). The dynamic balance between the oxidation system and antioxidation system is broken, and multiple reactive oxygen species (ROS) gather (Riba et al, 2017). As a major intracellular source of ROS, mitochondria are directly damaged by increased ROS, which affect the mitochondrial permeability (Circu and Aw, 2010). Apoptosis is induced dramatically with the consequence of damaged heart function (Ryter et al, 2007)

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