CV Science

Jeanne Mialet-Perez PhD Cardiac physiology

Course and current status

Current position : CRCN INSERM RESEARCHER at MITOVASC, team Mitolab

Université Angers, INSERMU1083, CNRS6015 (Director G. Lenaers)

Angers, france

Previous positions:

2005-2022: CR INSERM at I2MC (Institute of Metabolic and Cardiovascular Diseases), INSERM U1297, UNiversity of Toulouse, Toulouse, France

2002-2004: Post-doctoral fellow, Depatment of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA. (Director: Stephen Liggett)

1998-2002: Ph.D. , INSERM U446, Laboratory of Cellular and Molecular Cardiology, University Paris-Sud, Châtenay-Malabry, France. Director: Rodolphe Fischmeister.

Scientific summary

Jeanne Mialet-Perez leads a research axis on the molecular and cellular mechanisms that govern cardiomyocyte senescence, aging and heart failure (HF). HF is a major cause of death and hospitalization in subjects over 60 and its prevalence is constantly increasing due to the aging of the population. Our aim is to obtain a better understanding of altered signaling pathways in pathological cardiac agingg in order to identify new therapeutic targets. To achieve these goals, research programs range from molecular and cellular, to the most integrative levels of cardiac pathophysiology using in vivo models of HF and aging. Our research work has been pioneer in the study of the role of the mitochondrial enzyme monoamine oxidase-A (MAO-A) and its mechanisms of action in acute and chronic cardiac diseases (Santin, Aging Res Rev 2021). We have shown for the first time that increased expression of MAO-A in mouse heart, as observed in aging, led to chronic oxidative stress, energetic deficit, impairment of autophagic flux, cardiomyocyte necrosis and HF (Villeneuve C, ARS 2013; Santin Y, Cell Death Diff 2020; Santin Y, ARS 2016; Miceli C, Ox Med Cell Longev 2018). More recently, we showed in vitro that sustained MAO-A-dependent oxidative stress promoted DNA Damage Response (DDR) with the appearance of senescence markers (p53, p16, SA-bgal) (Manzella, Aging Cell 2018). Subsequently, further molecular analysis allowed us to identify non-canonical mechanisms of cardiomyocyte senescence. We observed that aged cardiomyocytes accumulated persistent damage in telomeric regions, promoted by mitochondrial dysfunction and responsible for the senescence phenotype (Anderson R, Embo J 2019). Importantly, pharmacological or genetic clearance of senescent cells in mice attenuated adverse features of cardiac aging such as hypertrophy and fibrosis (Anderson R, Embo J 2019) as well as post-ischemic damage (Dookun E, Aging Cell 2020). Altogether, this suggests that mitochondria play a major role in the cellular processes leading to pathological aging and/or HF. The research project within the Mitovasc Unit in Angers is dedicated to study mitochondrial health in order to understand how oxidative stress and alterations of the mitochondrial genome contribute to the age-related cardiac pathologies and to develop new therapeutic approaches for age-associated cardiac diseases.