sVEGFR-3 alleviates myocardial ischemia/reperfusion injury through regulating mitochondrial homeostasis and immune cell infiltration

Author:

Shang Liqun1,Ao Yuanhan1,Huang Xiaolin2,Wu Huawei3,Feng Kangni1,Wang Junjie1,Yue Yuan4,Zhou Zhuoming1,Liu Quan1,Li Huayang1,Fu Guangguo1,Liu Kaizheng1,Pan Jinyu1,Huang Yang1,Chen Jiantao1,Chen Guangxian1,Liang Mengya1,Yao Jianping1,Huang Suiqing1,Hou Jian1,Wu Zhongkai1

Affiliation:

1. First Affiliated Hospital of Sun Yat-sen University

2. Guangxi Medical University Cancer Hospital

3. Columbia University

4. Shenzhen people’s hospital

Abstract

Abstract

Recent studies have suggested that sVEGFR-3 is involved with cardiac disease by regulating lymphangiogenesis; however, results are inconsistent. The purpose of this study was to investigate the role and mechanism of sVEGFR-3 in myocardial ischemia/reperfusion injury (MI/RI). Plasma sVEGFR-3 levels were measured in patients with heart valve disease (HVD). sVEGFR-3 effects were evaluated in vivo in mice subjected to MI/RI, and in vitro using HL-1 cells exposed to hypoxia/reoxygenation. Echocardiography, TTC-Evans blue staining, ELISA, electron microscopy, immunofluorescence, Western blotting, and flow cytometry were used to investigate if sVEGFR3 attenuated I/R injury. TMT-based proteomics analysis was used to investigate the downstream mechanism of sVEGFR3. Results showed that plasma sVEGFR-3 levels were decreased in HVD patients compared to heathy control subjects. In patients undergoing cardiopulmonary bypass (CPB), sVEGFR-3 was significantly increased at 2 hours after release of the aortic cross-clamp and decreased slightly at 24 hours. In vivo, sVEGFR-3 pretreatment reduced cardiac dysfunction, infarct area, and myocardial injury indicators by reducing ROS production, apoptosis, and AIF expression. In vitro, sVEGFR-3 restored mitochondrial homeostasis by stabilizing the mitochondrial membrane potential (MMP) and preventing the opening of mitochondrial permeability transition pores (mPTP). And sVEGFR-3 inhibits mitochondrial apoptosis through the Ras/MEK/ERK pathway. Furthermore, I/R injury increased the proportion of M1 macrophages and CD4 + T cells in myocardial tissue, as well as serum IFN-γ and TNF-α levels, whereas sVEGFR-3 treatment attenuated these effects. sVEGFR-3 attenuates myocardial I/R injury by regulating mitochondrial homeostasis and immune cell infiltration, and reduces intrinsic ROS-mediated mitochondrial apoptosis via the Ras/MEK/ERK pathway.

Publisher

Springer Science and Business Media LLC

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3