Title: The implication of platelets in aortic valve calcification

Abstract:

Calcific aortic valve stenosis (AS) is the most prevalent valvular heart disease and the third most frequent cardiovascular disease after coronary artery disease and hypertension. Natural evolution of AS is characterized by a period of asymptomatic progressive valve calcification, which eventually leads to the development of a severe stenosis and to the onset of symptoms. Both in vivo and in vitro research has revealed that increased platelet activity is involved in the pathogenesis of AS, and can also be used as an indicator of AS severity. TGF-β1 enhances glycosaminoglycan (GAG) elongation, primarily located in the spongiosa layer of aortic valve, which increases lipid retention in the ECM. Lipid retention leads to the oxidation of lipid species which can activate the NF-κB pathway, leading to valve interstitial cells (VIC) osteogenic transition. Simultaneously, ADP released from activated platelets causes increased autotaxin (ATX) expression and release from VICs. ATX associates with platelets and ultimately assists in the conversion of lysophosphatidylcholine (LPC), a product of oxidized lipoproteins (Lp) and activated platelets, to lysophosphatidic acid (LPA). LPA binds to surface receptors on VICs causing signaling that activates the NF-κB pathway, leading to VIC osteogenic transition. Therefore, ADP released by activated platelets leads to LPA formation, enhanced by the availability of lipids retained in the ECM due to released TGF-𝛽𝛽1, which activates the NF-𝜅𝜅B pathway in VICs promoting osteogenic transition and thus mineralization of aortic valve.

Biography:

Rihab Bouchareb has completed her Ph.D. from Strasbourg University, France. She then achieved her postdoc at Heart and Lung Institute in Quebec, Canada. She is now an assistant professor at Mount Sinai, New York, USA. Her research is focused on the crosstalk between obesity and aortic valve calcification. She published over 30 publications published in international journals of high impact factors like European heart journal and Circulation; she attended and presented many presentations at international conferences.