Abstract 15914: Serotonin Related Gene Expression Patterns in Aortic Valve Interstitial Cells Are Altered by Proliferation and Serotonin Transporter Inhibition

• Published in: Circulation (New York, N.Y.) N.Y.), 2019-11, Vol.140 (Suppl_1 Suppl 1), p.A15914-A15914
• Main Authors: Aghali, Arbi, Keeney, Samuel J, Fitzpatrick, Emmett G, Shukla, Halley, Castillero, Estibaliz, Fishbein, Ilia, Ferrari, Giovanni, Levy, Robert J
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.140.suppl_1.15914

IntroductionSerotonin (5HT) has been observed to be associated with valvulopathies, with 5HT secreting carcinoid tumors and following administration with 5HT–pharmaceuticals, such as Fenfluramine. Relatively, little is known about anti–depressant drugs such as Fluoxetine (Flx) in terms of their potential for causing valvulopathies. Flx is a selective serotonin (5HT) reuptake inhibitor (SSRI) that prevents binding of 5HT to its transporter (SERT), consequently enhancing the signaling downstream of SERT and 5HT receptors.Hypothesis5HT related gene expression patterns in aortic valve interstitial cells (AVIC) are affected by proliferation and dysregulated by Flx.MethodsPig aortic valve leaflets were dissected from hearts obtained from an abattoir. AVIC were harvested, from left and right coronary aortic valve cusps, using collagenase, type II. At passage two to three, 80% confluent, cells were trypsinized, and divided into two groups. The control/non–treated group, and experimental group (treated with 1μM Flx), at a final seeding density 1.5 x 10 ml. At predetermined time–points, cells were lysed and RNA was extracted.ResultsAVIC grown under full serum conditions (10% fetal bovine serum) showed robust growth with nodule formation with or without Flx, by day 7 in all cultures. qRT–PCR results at 2 days and 7 days from AVIC grown without Flx demonstrated significant upregulation of HTR2A and COL1A2, and down regulation of SERT, VMAT2 and HTR2B. Flx treated AVIC demonstrated the same trends, but with dysregulation of all genes (see Table 1).Conclusion5HT related gene expression changes in proliferating AVIC are consistent with enhanced HTR2A signaling that is known to be associated with TGF–beta–1 related extracellular matrix production. Flx diminishes the extent of this change in gene expression patterns.