Jean-Sébastien Vartanian-Grimaldi , Zhenlin Li , Gaëlle Revet , Simon Alexandre , Nathalie Mougenot , Onnik Agbulut , Rodriguez Anne-Marie
{"title":"线粒体GTPase Miro1在心肌细胞功能和心脏稳态中的作用","authors":"Jean-Sébastien Vartanian-Grimaldi , Zhenlin Li , Gaëlle Revet , Simon Alexandre , Nathalie Mougenot , Onnik Agbulut , Rodriguez Anne-Marie","doi":"10.1016/j.acvd.2025.03.075","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Mitochondria, which are mainly abundant in cardiomyocytes and whose dysfunction has been widely observed in cardiovascular disease, are increasingly being considered as potential therapeutic targets. The function of mitochondria is closely linked to their ability to move along microtubules to adapt their distribution, morphology and dynamics in response to the demands of the cell. The outer mitochondrial membrane protein Miro1 is a key regulator of mitochondrial motility by promoting the anchorage of mitochondria to the kinesin/dynein motor of the microtubules on which they move. The role of Miro1 in cardiomyocytes remains largely unknown.</div></div><div><h3>Objective</h3><div>In this study, we explored the role of Miro1 in the heart using cardiomyocyte-specific deletion of Miro1 in adult mice.</div></div><div><h3>Method</h3><div>We disrupted Miro1 in the adult heart using a heart-specific tamoxifen-inducible Cre recombinase. Two and five weeks after tamoxifen injection, mice were characterized via echocardiography, comprehensive morphological evaluation, metabolic analysis, and transcriptomic profiling.</div></div><div><h3>Results</h3><div>The disruption of Miro1 led to impaired left ventricular function with reduced contractility, subsequently progressing to dilated cardiomyopathy, as demonstrated by serial echocardiography, including tissue Doppler imaging. The cytoarchitecture of cardiomyocytes was altered and display altered mitochondrial architecture. Interestingly, these alterations were associated with an increased fibrosis (assessed by Sirius red staining). These functional and structural defects were preceded by early alterations in the cardiac gene expression program: major decreases in mRNA levels for cardiac α-actin, muscle creatine kinase, and calcium-handling genes and increases in mRNA levels for stress-induced genes such as beta-myosin heavy chain genes, atrial natriuretic factor and brain natriuretic peptide.</div></div><div><h3>Conclusion</h3><div>These results highlight the importance of Miro1 in the maintenance of heart homeostasis and function.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S208"},"PeriodicalIF":2.3000,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Role of Miro1, the mitochondrial Rho GTPase, in cardiomyocyte function and heart homeostasis\",\"authors\":\"Jean-Sébastien Vartanian-Grimaldi , Zhenlin Li , Gaëlle Revet , Simon Alexandre , Nathalie Mougenot , Onnik Agbulut , Rodriguez Anne-Marie\",\"doi\":\"10.1016/j.acvd.2025.03.075\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><div>Mitochondria, which are mainly abundant in cardiomyocytes and whose dysfunction has been widely observed in cardiovascular disease, are increasingly being considered as potential therapeutic targets. The function of mitochondria is closely linked to their ability to move along microtubules to adapt their distribution, morphology and dynamics in response to the demands of the cell. The outer mitochondrial membrane protein Miro1 is a key regulator of mitochondrial motility by promoting the anchorage of mitochondria to the kinesin/dynein motor of the microtubules on which they move. The role of Miro1 in cardiomyocytes remains largely unknown.</div></div><div><h3>Objective</h3><div>In this study, we explored the role of Miro1 in the heart using cardiomyocyte-specific deletion of Miro1 in adult mice.</div></div><div><h3>Method</h3><div>We disrupted Miro1 in the adult heart using a heart-specific tamoxifen-inducible Cre recombinase. Two and five weeks after tamoxifen injection, mice were characterized via echocardiography, comprehensive morphological evaluation, metabolic analysis, and transcriptomic profiling.</div></div><div><h3>Results</h3><div>The disruption of Miro1 led to impaired left ventricular function with reduced contractility, subsequently progressing to dilated cardiomyopathy, as demonstrated by serial echocardiography, including tissue Doppler imaging. The cytoarchitecture of cardiomyocytes was altered and display altered mitochondrial architecture. Interestingly, these alterations were associated with an increased fibrosis (assessed by Sirius red staining). These functional and structural defects were preceded by early alterations in the cardiac gene expression program: major decreases in mRNA levels for cardiac α-actin, muscle creatine kinase, and calcium-handling genes and increases in mRNA levels for stress-induced genes such as beta-myosin heavy chain genes, atrial natriuretic factor and brain natriuretic peptide.</div></div><div><h3>Conclusion</h3><div>These results highlight the importance of Miro1 in the maintenance of heart homeostasis and function.</div></div>\",\"PeriodicalId\":55472,\"journal\":{\"name\":\"Archives of Cardiovascular Diseases\",\"volume\":\"118 6\",\"pages\":\"Page S208\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-05-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of Cardiovascular Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1875213625001706\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Cardiovascular Diseases","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1875213625001706","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Role of Miro1, the mitochondrial Rho GTPase, in cardiomyocyte function and heart homeostasis
Introduction
Mitochondria, which are mainly abundant in cardiomyocytes and whose dysfunction has been widely observed in cardiovascular disease, are increasingly being considered as potential therapeutic targets. The function of mitochondria is closely linked to their ability to move along microtubules to adapt their distribution, morphology and dynamics in response to the demands of the cell. The outer mitochondrial membrane protein Miro1 is a key regulator of mitochondrial motility by promoting the anchorage of mitochondria to the kinesin/dynein motor of the microtubules on which they move. The role of Miro1 in cardiomyocytes remains largely unknown.
Objective
In this study, we explored the role of Miro1 in the heart using cardiomyocyte-specific deletion of Miro1 in adult mice.
Method
We disrupted Miro1 in the adult heart using a heart-specific tamoxifen-inducible Cre recombinase. Two and five weeks after tamoxifen injection, mice were characterized via echocardiography, comprehensive morphological evaluation, metabolic analysis, and transcriptomic profiling.
Results
The disruption of Miro1 led to impaired left ventricular function with reduced contractility, subsequently progressing to dilated cardiomyopathy, as demonstrated by serial echocardiography, including tissue Doppler imaging. The cytoarchitecture of cardiomyocytes was altered and display altered mitochondrial architecture. Interestingly, these alterations were associated with an increased fibrosis (assessed by Sirius red staining). These functional and structural defects were preceded by early alterations in the cardiac gene expression program: major decreases in mRNA levels for cardiac α-actin, muscle creatine kinase, and calcium-handling genes and increases in mRNA levels for stress-induced genes such as beta-myosin heavy chain genes, atrial natriuretic factor and brain natriuretic peptide.
Conclusion
These results highlight the importance of Miro1 in the maintenance of heart homeostasis and function.
期刊介绍:
The Journal publishes original peer-reviewed clinical and research articles, epidemiological studies, new methodological clinical approaches, review articles and editorials. Topics covered include coronary artery and valve diseases, interventional and pediatric cardiology, cardiovascular surgery, cardiomyopathy and heart failure, arrhythmias and stimulation, cardiovascular imaging, vascular medicine and hypertension, epidemiology and risk factors, and large multicenter studies. Archives of Cardiovascular Diseases also publishes abstracts of papers presented at the annual sessions of the Journées Européennes de la Société Française de Cardiologie and the guidelines edited by the French Society of Cardiology.