Team: Lipoproteins and mitochondrial adaptations in Age-related vascular & metabolic diseases (LiMitAging - Dir: L. Martinez) - New website coming soon !
The aging process affects numerous organs, including the liver (non-alcoholic steatohepatitis or NASH) and the cardiovascular system (endothelial dysfonction), leading to cardiometabolic diseases. Aging biology research has revealed different molecular pathways involved in the aging process and pointed out mitochondrial as one of the key regulator of longevity. Particularly, mitochondrial dysfunction drives cellular senescence and a deterioration of respiratory chain activity is associated with aging in mammals.
The project of the LiMitAging team is to study the relation between some actors of mitochondrial functions and aging, and is driven by the hypothesis that enhancing mitochondrial health and mitochondrial quality-control mechanisms will promote healthy aging.
Our expertise in the field of lipoprotein and mitochondria led us to identify original actors associated to lipid and mitochondrial energy metabolism.
Our objectives are to explore the physiological and pathophysiological roles of those molecular actors that regulate:
1) The respiratory chain complex V, also called ATP synthase
2) Autophagy, particularly mitophagy
3) Ectopic ATP synthase and G protein-coupled P2Y receptors signaling pathways
Our research has led to the development of original drug candidates and biomarkers that are currently being validated on preclinical models and cohorts, to be used for early detection and resolution of mitochondrial dysfunctions in pre-frail individuals or in population at high risk of cardiometabolic diseases.
To summarize, our projects use unique genetic and pharmacological approaches to explore mitochondrial-mediated mechanisms of aging, with the ultimate goal to restore or enhance mitochondrial functions, limit aging process and benefit cardiometabolic health.
The LiMitAging team participates in the large regional Inspire program on healthy aging, launched in 2019. The Inspire consortium brings together the Gérontopôle of the Toulouse University Hospital and several research laboratories which have decided to combine their expertise to address key biological components (immunity, inflammation, metabolism, repair mechanisms) present in all organs, essential for their functioning and altered during aging.
Projects are funded by the European Regional Development Fund (FEDER - THERANOVASC), Région Occitanie (THERANOVASC, HEPATOCARE), Fondation de France (FDF) and French National Research Agency (ANR).
Press release (03/06/2020) - Maladies cardio-vasculaires: des Toulousain proposent de mieux doser le "bon" cholestérol.
Team: Phosphoinositide 3-kinase in cardiovascular diseases: From molecular mechanisms to new therapeutic approaches.
Phosphoinositide 3-kinases (PI3K) generate lipid second messengers that control a wide range of biological processes such as survival, growth, metabolism or cell migration. Thus, PI3K pathways deregulations are found in several diseases including cardiovascular diseases (CVD). In multicellular organisms, this family of kinases is divided in 3 classes based on structural and biochemical characteristics: Classes IA and IB, II and III. Recent evidences demonstrate that they exert non-redundant and opposite functions. Whereas class Ia enzymes control transcriptional and survival pathways through AKT signaling and block autophagy through mTOR activation, the class III (Vps34) is an indispensable actor of cell trafficking and autophagy. Thus, more than 25 years after their discovery, their involvement in autophagy and cell regulation makes PI3K attractive targets to modulate cell homeostasis especially in vascular cells.
Our projects propose to decipher signaling pathways involving these kinases in control of endothelial and smooth muscle cell homeostasis in response to arterial stress including mechanical and oxidative stress. Our research is divided in three main axis:
1- Mechanisms involved in EC homeostasis and especially the role of class II PI3K in primary cilium/autophagy
2 - Investigation of class I PI3K dysregulation in Smooth Muscle Cells dysfunction in disturbed metabolic conditions
3 - Evaluation of new therapeutic strategies targeting PI3K/mTOR for arterial devices to prevent complication of atherosclerosis treatment in high-risk population of CVD.
Thus, our aim is to translate our fundamental research into clinical perspectives thanks to a close collaboration with the interventional cardiology department of CHU. Combining fundamental, physiopathology and clinical approaches, this research axis aims to better understand the cellular responses involved in atherosclerosis and its complications in order to discover new therapeutic approaches in cardiovascular diseases.