Comparison of Serotonin-Regulated Calcific Processes in Aortic and Mitral Valvular Interstitial Cells

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dc.creatorWang, Xinmei
dc.creatorDeb, Nandini (TTU)
dc.creatorLacerda, Carla M. R. (TTU)
dc.date.accessioned2022-11-29T22:42:26Z
dc.date.available2022-11-29T22:42:26Z
dc.date.issued2021
dc.description© 2021 The Authors. Published by American Chemical Society. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.en_US
dc.description.abstractCalcification is an important pathological process and a common complication of degenerative valvular heart diseases, with higher incidence in aortic versus mitral valves. Two phenotypes of valvular interstitial cells (VICs), activated VICs and osteoblastic VICs (obVICs), synergistically orchestrate this pathology. It has been demonstrated that serotonin is involved in early stages of myxomatous mitral degeneration, whereas the role of serotonin in calcific aortic valve disease is still unknown. To uncover the link between serotonin and osteogenesis in heart valves, osteogenesis of aortic and mitral VICs was induced in vitro. Actin polymerization and serotonin signaling were inhibited using cytochalasin D and serotonin inhibitors, respectively, to investigate the role of cell activation and serotonin signals in valvular cell osteogenesis. To evaluate calcification progress, calcium and collagen deposits along with the expression of protein markers, including the rate-limiting enzyme of serotonin synthesis [tryptophan hydroxylase 1 (TPH1)], were assessed. When exposed to osteogenic culture conditions and grown on soft surfaces, passage zero aortic VICs increased extracellular collagen deposits and obVIC phenotype markers. A more intense osteogenic process was observed in aortic VICs of higher passages, where cells were activated prior to osteogenic induction. For both, TPH1 expression was upregulated as osteogenesis advanced. However, these osteogenic changes were reversed upon serotonin inhibition. This discovery provides a better understanding of signaling pathways regulating VIC phenotype transformation and explains different manifestations of degenerative pathologies. In addition, the discovery of serotonin-based inhibition of valvular calcification will contribute to the development of potential novel therapies for calcific valvular diseases.en_US
dc.identifier.citationWang, X., Deb, N., & Lacerda, C. M. (2021). Comparison of serotonin-regulated calcific processes in aortic and mitral valvular interstitial cells. ACS Omega, 6(30), 19494–19505. https://doi.org/10.1021/acsomega.1c01723en_US
dc.identifier.urihttps://doi.org/10.1021/acsomega.1c01723
dc.identifier.urihttps://hdl.handle.net/2346/90368
dc.language.isoengen_US
dc.subjectAnatomyen_US
dc.subjectBiopolymersen_US
dc.subjectCalciumen_US
dc.subjectInhibitorsen_US
dc.subjectNeurophysiologyen_US
dc.titleComparison of Serotonin-Regulated Calcific Processes in Aortic and Mitral Valvular Interstitial Cellsen_US
dc.typeArticleen_US

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