34- EA 7296 - L. Monassier
The main research areas of the team
This part of our group is interested in the role played by peripheral serotonin, especially that is released by blood platelets, in the repair process and the structural changes of cardiovascular tissues. We were able to demonstrate that a sub-type of serotonin receptor, the 5-HT2B receptor, is involved in cardiac development during early embryogenesis, but also takes part in the development of cardiomyocyte hypertrophy by regulating the release of inflammatory cytokines and cytokines involved in the changes of the extracellular matrix from interstitial cells. Having concentrated for several years on the remodelling of the left ventricular tissue, our group now mainly researches the involvement of this same receptor in the changes of the structure of the heart valves. Indeed the 5-HT2B receptor is the target of a "medicine" well known for inducing valvulopathy: Mediator®.
Historically, our laboratory is interested in the role of the imidazoline receptors in regulating sympathetic nervous activity. Within the team, we have synthesised a complete series of molecules that are the subject of a patent owned by the University and from which we are deriving value with SATT Conectus. Globally, this project aims at studying the effects of these original molecules in a complex clinical syndrome known as the "Metabolic Syndrome" and which includes several symptoms such as dyslipidemias, arterial hypertension and glucose intolerance. We have been able to highlight some particularly unusual effects of these substances that make them good candidates for future drugs for treating this metabolic syndrome.
Our team was able to highlight the overexpression of muscarinic receptors in the hearts of infants who have died from sudden infant death syndrome. This abnormality has also been identified in an experimental rabbit model, of which we have the exclusivity. All our research in this area currently aims at demonstrating this abnormality in children and adults displaying vagal hyperactivity. The expression of muscarinic receptors is studied here in the white blood cells with the aim of developing a biological test for identifying children at risk so as to be able to propose heart rate monitoring and/or pharmacological treatment for reducing bradycardia due to the parasympathetic system.
EA 7296 Unistra
Director: Laurent MONASSIER
- Old spontaneously hypertensive rats gather together typical features of human chronic left-ventricular dysfunction with preserved ejection fraction. Marzak H, Ayme-Dietrich E, Lawson R, Mokni W, Combe R, Becker J, Fertak LE, Champy MF, Monassier L. J Hypertens. 2014; 32(6):1307-16.
- Prevention and reversal of severe mitochondrial cardiomyopathy by gene therapy in a mouse model of Friedreich's ataxia. Perdomini M, Belbellaa B, Monassier L, Reutenauer L, Messaddeq N, Cartier N, Crystal RG, Aubourg P, Puccio H. Nat Med. 2014;20(5):542-7.
- Methylation of imidazoline related compounds leads to loss of α(2)-adrenoceptor affinity. Synthesis and biological evaluation of selective I(1) imidazoline receptor ligands. Schann S, Greney H, Gasparik V, Dontenwill M, Rascente C, Lacroix G, Monassier L, Bruban V, Feldman J, Ehrhardt JD, Bousquet P. Bioorg Med Chem. 2012 1 ; 20(15) : 4710-4715
- Contribution of gene-modified mice and rats to our understanding of the cardiovascular pharmacology of serotonin. Monassier L, Laplante MA, Ayadi T, Doly S, Maroteaux L. Pharmacol Ther. 2010 Dec;128(3):559-67.
- The purinergic P2Y1 receptor supports leptin secretion in adipose tissue. Laplante MA, Monassier L (co author), Freund M, Bousquet P, Gachet C. Endocrinology. 2010 May 151(5):2060-70.
- Serotonin and angiotensin receptors in cardiac fibroblasts coregulate adrenergic-dependent cardiac hypertrophy. Jaffré F, Bonnin P, Callebert J, Debbabi H, Setola V, Doly S, Monassier L, Mettauer B, Blaxall BC, Launay JM, Maroteaux L. Circ Res. 2009 Jan 2;104(1):113-23.
- Serotonin 5-HT(2B) receptor blockade prevents reactive oxygen species-induced cardiac hypertrophy in mice. Monassier L, Laplante MA, Jaffré F, Bousquet P, Maroteaux L, de Champlain J. Hypertension. 2008 Aug;52(2):301-7.
- Improvement of cardiac diastolic function by long-term centrally mediated sympathetic inhibition in one-kidney, one-clip hypertensive rabbits. Signolet IL, Bousquet PP, Monassier L. Am J Hypertens. 2008 Jan;21(1):54-60.
- sigma(2)-receptor ligand-mediated inhibition of inwardly rectifying K(+) channels in the heart. Monassier L, Manoury B, Bellocq C, Weissenburger J, Greney H, Zimmermann D, Ehrhardt JD, Jaillon P, Baró I, Bousquet P. J Pharmacol Exp Ther. 2007 Jul;322(1):341-50.
- Involvement of the serotonin 5-HT2B receptor in cardiac hypertrophy linked to sympathetic stimulation: control of interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha cytokine production by ventricular fibroblasts. Jaffré F, Callebert J, Sarre A, Etienne N, Nebigil CG, Launay JM, Maroteaux L, Monassier L. Circulation. 2004 Aug 24;110(8):969-74.