0171 : Contribution of progenitor cells sharing some serotonergic proteins in the pathophysiology of human aortic and mitral valves degeneration

Abstract

Many compounds (pergolide, fenfluramine, ectasy) were described as inducers of fibrotic valvular lesions. All these compounds share in common to activate the 5HT2B serotonergic receptor. This observation leads to the hypothesis that cardiac valves express a « serotonergic system » that could be activated by serotonin (5-HT) or 5-HT receptor (5-HTR) agonists. In this work, we characterized the expression pattern of 5-HT2A, 2B, 4 R and the 5- HT transporter (SERT) in whole and cell subpopulations of 30 human mitral and aortic valves collected at the time of surgical valve replacement (Aortic: 11 calcified, 5 sclerotic, 4 bicuspid; Mitral: 12 dystrophic). All samples express 5HT2A, 2B, 4 R and SERT, the amount of 5HT2B R mRNA being higher than the 5HT2A R whatever the valve and etiology. 5HT2BR expression is found in endothelial cells (CD31+) at the valve surface, but also inside valve lesions, expressed by interstitial cells (smooth muscle α-actin and vimentin positive cells) located in an abundant glycosaminoglycan matrix. In fact, fibromyxoid lesions and calcified aortic valves express a high amount of CD34+ cells. These cells are endothelial progenitors because they express VEGFR2 and eNOS together with 5-HT2R. After collagenase treatment, valve samples were labeled with CD31 and CD34 antibodies: 60.1 (± 11) % of all mitral valvular cells are CD34+ compared to 36.1 (±8) % of aortic valvular cells (FACS analysis and sorting). To summarize, 5HT2A, 2B, 4 receptors and SERT are expressed in aortic and mitral diseased valves. The amounts of 5HT2A, 2B R mRNA are equivalent between mitral and aortic valves. High amount of CD34+ endothelial progenitors, expressing 5HT2AR and 5HT2BR, are found in degenerated valves. The contribution of the two 5-HT2 receptors and endothelial progenitors in valve degeneration is now under investigation.