Mitogenic and secretory responses of human valve interstitial cells to vasoactive agents.

Background and Aim of the Study: The vasoactive agent 5-hydroxytryptamine (5-HT) has been implicated in valve disease due to possible trophic effects on valve interstitial cells (IC). The present study was aimed at characterizing the responses of cultured human heart valve IC to 5-HT in terms of intracellular calcium concentration ([Ca2+]i), mitogenesis and collagen synthesis. The effects of angiotensin II (Ang II) were also studied in parallel. Methods: IC were obtained by collagenase digestion of valve leaflets isolated from transplant recipient hearts. Changes in [Ca2+]i were measured from fluorescence of the ratiometric calcium dye, fura 2. Mitogenic and collagen synthetic responses of valve IC were measured by 3H-thymidine incorporation (DNA synthesis) and 3H-proline incorporation assays respectively, in quiescent cells. Results: Human valve IC responded to 5-HT and Ang II with mean maximal increases in [Ca2+]i of 249 +/- 47 nM and 397 +/- 159 nM, respectively. 5-HT stimulated DNA synthesis in quiescent IC, although to varying degrees among different isolations, with a maximum 43.4 +/- 20.1% increase by 10(-7) M 5-HT (p