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

• 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
• 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

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 据估计，2017年诊断出310万例心肌炎/心肌病。患有疾病的患者 心肌炎有急性心力衰竭导致猝死的风险，心肌炎的发生率和严重程度是 男性高于女性。运动通常改善心脏功能；然而，在病毒性心肌炎期间 运动可导致心力衰竭，导致目前的指南建议患者戒酒 确诊后运动3~6个月。肠道病毒包括柯萨奇病毒B3(CVB3)是一种常见的 美国心肌炎的起因。尽管30年前发表的几项研究发现，锻炼增加了 病毒性心肌炎小鼠的病毒复制和死亡，最近没有研究检查心脏的原因 运动后的失败。我们最近发表了一篇文章，指出在正常健康的小鼠中，运动可以诱导线粒体 通过β1肾上腺素能受体(AR)信号分裂导致线粒体碎裂(即更小、更多 圆形)，与久坐不动的小鼠相比，能量产生增强。此外，我们发现CVB3 需要线粒体分裂才能复制病毒。这项提案的总体目标是确定性行为是否 β-1AR诱导心肌细胞线粒体分裂与运动的差异 心肌炎导致病毒复制增加，线粒体功能障碍，心肌细胞死亡，以及 生物能量衰竭导致心力衰竭。

项目成果

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
• 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

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