Sex differences in exercise-induced mitochondrial function during viral myocarditis

病毒性心肌炎期间运动诱发的线粒体功能的性别差异

基本信息

批准号：
10227233
负责人：
DeLisa Fairweather
金额：
$ 11.36万
依托单位：
MAYO CLINIC JACKSONVILLE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10227233
关键词：
Acute Adrenergic Receptor Adult Age Autoimmune Bioenergetics Cardiac Cardiac Myocytes Cardiomyopathies Cardiovascular Physiology Cell Death Cessation of life Child Consumption Coxsackie Viruses Data Diagnosis Enterovirus Exercise Failure Fright Goals Gonadal Steroid Hormones Guidelines Health Benefit Heart Heart Injuries Heart failure In Vitro Incidence Infection Inflammation Lead Mediating Membrane Potentials Mitochondria Modeling Mus Myocardial Myocarditis Paper Patients Physiological Play Production Publishing Receptor Signaling Reporting Research Personnel Risk Role Severities Sex Differences Signal Transduction Sudden Death Viral Virus Diseases Virus Replication Woman cell injury extracellular vesicles heart function human disease improved male men mitochondrial dysfunction mortality novel prevent response sedentary sex sudden cardiac death targeted treatment viral myocarditis

项目摘要

PROJECT SUMMARY/ABSTRACT An estimated 3.1 million cases of myocarditis/cardiomyopathy were diagnosed in 2017. Patients with myocarditis are at risk of sudden death from acute heart failure and the incidence and severity of myocarditis is higher in men than women. Exercise typically improves cardiac function; however, during viral myocarditis exercise can precipitate heart failure leading to current guidelines recommending that patients abstain from exercise for 3-6 months after diagnosis. Enteroviruses including coxsackievirus B3 (CVB3) are a common cause of myocarditis in the US. Although several studies published 30 years ago found that exercise increased viral replication and death in mice with viral myocarditis, no recent studies have examined the reason for heart failure following exercise. We recently published that in normal, healthy mice exercise induces mitochondrial fission through β1 adrenergic receptor (AR) signaling resulting in fragmented mitochondria (i.e., smaller, more circular) with enhanced energy production compared to sedentary mice. Additionally, we found that CVB3 requires mitochondrial fission for viral replication. The overall goal of this proposal is to determine whether sex differences in β1AR-induced mitochondrial fission with exercise in cardiomyocytes or mice with CVB3 myocarditis lead to increased viral replication, mitochondrial dysfunction, cardiomyocyte cell death, and bioenergetic failure resulting in heart failure.

项目摘要/摘要 2017年诊断出估计有310万例心肌炎/心肌病病例。患有心肌炎有急性心力衰竭突然死亡的风险，心肌炎的事件和严重程度是男性高于女人。运动通常改善心脏功能；但是，在病毒心肌炎期间运动会导致心力衰竭导致当前指南建议患者戒烟诊断后3-6个月运动。肠道病毒包括Coxsackievivirus B3（CVB3）很常见美国心肌炎的原因。尽管30年前发表的几项研究发现运动有所增加病毒心肌炎的小鼠病毒复制和死亡，最近没有研究检查心脏的原因运动后的失败。我们最近发表了，在正常的健康小鼠中，运动会诱导线粒体通过β1肾上腺素受体（AR）信号的裂变导致线粒体碎片（即较小，更多）与久坐小鼠相比，圆形的能量产生增强。此外，我们发现CVB3 需要线粒体裂变才能复制。该提议的总体目标是确定是否性 β1AR诱导的线粒体裂变在心肌细胞或CVB3中的小鼠中的差异心肌炎导致病毒复制增加，线粒体功能障碍，心肌细胞死亡和生物能衰竭导致心力衰竭。

项目成果

期刊论文数量（22）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Sex and age differences in sST2 in cardiovascular disease.

DOI：
10.3389/fcvm.2022.1073814
发表时间：
2022
期刊：
Frontiers in cardiovascular medicine
影响因子：
3.6
作者：
通讯作者：

The Effect of Convalescent Plasma Therapy on COVID-19 Patient Mortality: Systematic Review and Meta-analysis.

DOI：
10.1101/2020.07.29.20162917
发表时间：
2021-02-02
期刊：
medRxiv : the preprint server for health sciences
影响因子：
0
作者：
Klassen, Stephen A;Senefeld, Jonathon;Joyner, Michael J
通讯作者：
Joyner, Michael J

Platforms for Personalized Polytherapeutics Discovery in COVID-19.

DOI：
10.1016/j.jmb.2021.166945
发表时间：
2021-05-14
期刊：
Journal of molecular biology
影响因子：
5.6
作者：
Hopkins C;Onweni C;Zambito V;Fairweather D;McCormick K;Ebihara H;Caulfield T;Zhang YS;Freeman WD
通讯作者：
Freeman WD

In Reply - Limitations of Safety Update on Convalescent Plasma Transfusion in COVID-19 Patients.

DOI：
10.1016/j.mayocp.2020.09.032
发表时间：
2020-12
期刊：
Mayo Clinic proceedings
影响因子：
8.9
作者：
Joyner MJ;Senefeld JW;Klassen SA;Fairweather D;Wright RS;Carter RE
通讯作者：
Carter RE

COVID-19 Convalescent Plasma Is More than Neutralizing Antibodies: A Narrative Review of Potential Beneficial and Detrimental Co-Factors.

DOI：
10.3390/v13081594
发表时间：
2021-08-11
期刊：
Viruses
影响因子：
0
作者：
Focosi D;Franchini M;Pirofski LA;Burnouf T;Fairweather D;Joyner MJ;Casadevall A
通讯作者：
Casadevall A