top of page
IMG_0952.jpeg

Lipoproteins and Mitochondrial adaptations in Age-related vascular & metabolic diseases (LiMitAging)

logotype_i2mc.png

Our project aims to study the mechanism of action and the function of some players involved in lipoprotein metabolism and mitochondrial function, in different physiopathological contexts (aging, atherogenic dyslipidemia, hepatic and vascular dysfunctions).
Our objectives are to explore the physiological and pathophysiological roles of those molecular actors that regulate:
1) The oxidative phosphorylation, in particular the mitochondrial ATP synthase
2) The autophagy, in particular the mitophagy, and the involvement of this process in inter-organelle crosstalk
3) The cell surface 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 (cells, organoids, animals) and human cohorts, to be used for early detection and resolution of mitochondrial dysfunctions and metabolic disorders in elderly with risk of functional decline or in population at high risk of cardiometabolic diseases.

Martinez.png

Laurent Martinez

Inserm Research Director

laurent.martinez@inserm.fr

Technical skills: Transgenic mouse models for P2Y receptors

In-vitro and in-vivo mouse analysis of endothelial function (e.g. nitric oxide production, endothelial healing, aortic ring vasorelaxation); Mouse models of NASH and metabolic syndrome; Cohorts of Coronary Heart Disease patients; Lipoproteins and apolipoproteins isolation and quantification; assesment of mitochondrial energy metabolism

References:

 

Horckmans M, Diaz Villamil E, Verdier C, Laurell H, Ruidavets JB, De Roeck L, Combes G, Martinez LO, Communi D. Loss-of-function N178T variant of the human P2Y4 receptor is associated with decreased severity of coronary artery disease and improved glucose homeostasis. Front Pharmacol. 2022 Dec 2;13:1049696. doi: 10.3389/fphar.2022.1049696. PMID: 36532779

Cabou C, Martinez LO. The Interplay of Endothelial P2Y Receptors in Cardiovascular Health: From Vascular Physiology to Pathology. Int J Mol Sci. 2022 May 24;23(11):5883. doi: 10.3390/ijms23115883. PMID: 35682562

Cabou C, Honorato P, Briceño L, Ghezali L, Duparc T, León M, Combes G, Frayssinhes L, Fournel A, Abot A, Masri B, Parada N, Aguilera V, Aguayo C, Knauf C, González M, Radojkovic C, Martinez LO. Pharmacological inhibition of the F1-ATPase/P2Y1 pathway suppresses the effect of apolipoprotein A1 on endothelial nitric oxide synthesis and vasorelaxation. Acta Physiol (Oxf). 2019 Jul;226(3):e13268. doi: 10.1111/apha.13268. PMID: 30821416.

Werder RB, Ullah MA, Rahman MM, Simpson J, Lynch JP, Collinson N, Rittchen S, Rashid RB, Sikder MAA, Handoko HY, Curren BF, Sebina I, Hartel G, Bissell A, Ngo S, Yarlagadda T, Hasnain SZ, Lu W, Sohal SS, Martin M, Bowler S, Burr LD, Martinez LO, Robaye B, Spann K, Ferreira MAR, Phipps S. Targeting the P2Y13 Receptor Suppresses IL-33 and HMGB1 Release and Ameliorates Experimental Asthma. Am J Respir Crit Care Med. 2022 Feb 1;205(3):300-312. doi: 10.1164/rccm.202009-3686OC. PMID: 34860143.

Verdier C, Ruidavets JB, Genoux A, Combes G, Bongard V, Taraszkiewicz D, Galinier M, Elbaz M, Ferrières J, Martinez LO, Perret B. Common p2y13 polymorphisms are associated with plasma inhibitory factor 1 and lipoprotein(a) concentrations, heart rate and body fat mass: The GENES study. Arch Cardiovasc Dis. 2019 Feb;112(2):124-134. doi: 10.1016/j.acvd.2018.09.003. PMID: 30600215.

Travaillons ensemble

Contactez-nous pour que nous puissions travailler ensemble.

  • Facebook
  • Twitter
  • LinkedIn
  • Instagram
Merci pour votre envoi !
bottom of page