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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.

项目总结/摘要据估计，2017年诊断出310万例心肌炎/心肌病。患者心肌炎有急性心力衰竭猝死的危险，心肌炎的发病率和严重程度男性高于女性。运动通常可以改善心脏功能;然而，在病毒性心肌炎期间，运动可以加速心力衰竭，导致目前的指南建议患者放弃运动。确诊后3-6个月进行锻炼。包括柯萨奇病毒B3（CVB 3）在内的肠道病毒是常见的心肌炎的病因在美国尽管30年前发表的几项研究发现，病毒复制和死亡的小鼠与病毒性心肌炎，没有最近的研究已经审查的原因，心脏失败后的练习我们最近发表的研究表明，在正常健康的小鼠中，运动诱导线粒体通过β1肾上腺素能受体（AR）信号传导的分裂导致片段化的线粒体（即，小更圆形），与久坐小鼠相比具有增强的能量产生。此外，我们发现CVB 3 病毒复制需要线粒体分裂这项提案的总体目标是确定性行为是否 β 1AR诱导心肌细胞或CVB 3小鼠运动时线粒体分裂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，导致心力衰竭的生物能量衰竭。

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）

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

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

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：

A Case-Control Study of Peripartum Cardiomyopathy Using the Rochester Epidemiology Project.

使用Rochester流行病学项目对周围心肌病的病例对照研究。

DOI：
10.1016/j.cardfail.2020.12.021
发表时间：
2021-03
期刊：
Journal of cardiac failure
影响因子：
6
作者：
Douglass EJ;Cooper LT Jr;Morales-Lara AC;Adedinsewo DA;Rozen TD;Blauwet LA;Fairweather D
通讯作者：
Fairweather D

Trpc6 Promotes Doxorubicin-Induced Cardiomyopathy in Male Mice With Pleiotropic Differences Between Males and Females.

DOI：
10.3389/fcvm.2021.757784
发表时间：
2021
期刊：
Frontiers in cardiovascular medicine
影响因子：
3.6
作者：
Norton N;Bruno KA;Di Florio DN;Whelan ER;Hill AR;Morales-Lara AC;Mease AA;Sousou JM;Malavet JA;Dorn LE;Salomon GR;Macomb LP;Khatib S;Anastasiadis ZP;Necela BM;McGuire MM;Giresi PG;Kotha A;Beetler DJ;Weil RM;Landolfo CK;Fairweather D
通讯作者：
Fairweather D