Group leaders: Catherine BOILEAU & Guillaume JONDEAU
Staff of the team
|ABOU KHLIL Yara||Master 2|
|ARNAUD Pauline||AHU||01.40.25.85.55 / firstname.lastname@example.org|
|BOILEAU Catherine||PU-PH||01.40.25.75.21 / email@example.com|
|EL KHOURY Petra||Post Docfirstname.lastname@example.org|
|GRANGE Thomas||Master 2|
|MAMAN Esther||Master 2|
|MESSIKA-ZEITOUN David||PHUemail@example.com / firstname.lastname@example.org|
|RABES Jean-Pierre||MCUPH||01.49.09.55.97 / email@example.com / firstname.lastname@example.org|
Aortic root and aortic valves share numerous common structural, physiological, genetic, and pathophysiologic features. Aortic root and heart valves are vascular tissues highly enriched with fibrillar insoluble extracellular matrix components, including proteoglycans, elastin, and collagen — in situ synthesized by stromal cells : myofibroblasts in valves, smooth muscle cells in aorta. Both tissues support the elevated mechanical stress generated by hemodynamics in the human body, including physiological vortices in the valsalva sinus during diastole (depicted by Leornardo Da Vinci 500 years ago; figure) and the impact of the systolic ejected flow on the aortic root. As a consequence, aortic root and valves pathologies share common etiologies including monogenic heritable diseases, such as Marfan syndrome, which is recognized as a pathogenic determinant of aneurysms and dissections of the ascending aorta, but also of valve structural abnormality and dysfunction. In parallel, bicuspid aortic valve, a highly frequent congenital anomaly, is an important anatomic risk factor for development of aortic valve stenosis but also of aneurysms and/or dissections of the aortic root. Structural diseases of aortic root, aneurysms and dissections, and heart valves, stenosis and calcifications, share the common histological feature of areas of mucoid degeneration, determined by genomic/ hemodynamic microenvironment in both these tissues. For example, aneurysms preferentially develop in valsalva sinus in response to Marfan mutations, in relation to physiological vortices, whereas aneurysms develop in the aortic root in bicuspids, in relation to the change of the aortic ring geometry (oval versus round).
Our project is to pursue the discovery of new genes and of genetic modifiers involved in aortic root and valve diseases in human, to decipher the common and different pathophysiology of these diseases, to develop new diagnostic (functional and molecular imaging) and interventional therapeutics and to decrypt the interactions between aortic valves and aortic root.
The new team 2 originated from Team 6 of U698 (C Boileau) with the addition for the valvular disease project of D Messika-Zeitoun, Alec Vahanian, B Iung – new members – and D Himbert (PH) and MP Jacob (DR2 CNRS) from previous teams 5 and 2, respectively.