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

Area of Science:

• Cardiovascular Biology
• Cellular Pathophysiology
• Biomaterials Science

Background:

• Calcification is a key pathological process in degenerative valvular heart diseases, predominantly affecting aortic valves.
• Valvular interstitial cells (VICs) exist in activated and osteoblastic (obVIC) phenotypes, jointly driving valve calcification.
• Serotonin's role in myxomatous mitral degeneration is known, but its involvement in calcific aortic valve disease remains unclear.

Purpose of the Study:

• To investigate the link between serotonin signaling and osteogenesis in aortic and mitral VICs.
• To determine the role of cell activation and serotonin in valvular osteogenesis.
• To explore potential therapeutic strategies targeting serotonin pathways for calcific valvular diseases.

Main Methods:

• Osteogenesis was induced in vitro for aortic and mitral VICs.
• Actin polymerization and serotonin signaling were inhibited using cytochalasin D and serotonin inhibitors.
• Calcium and collagen deposits, protein marker expression (including TPH1), and VIC phenotype changes were assessed.

Main Results:

• Aortic VICs exhibited increased collagen and obVIC markers under osteogenic conditions, with enhanced osteogenesis in higher passage cells.
• TPH1 expression was upregulated with advancing osteogenesis in VICs.
• Inhibition of serotonin signaling reversed osteogenic changes and reduced calcification.

Conclusions:

• Serotonin signaling plays a crucial role in promoting osteogenesis and calcification in VICs.
• Understanding serotonin's role provides insights into VIC phenotype transformation and degenerative valve pathologies.
• Serotonin inhibition presents a promising therapeutic avenue for treating calcific valvular diseases.