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

Background and aim of the study: The vasoactive agent Ei-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 character izing the responses of cultured human heart valve IC to 5-HT in terms of in tracellular calcium concentration ([Ca2+](i)), mitogenesis and collagen syn thesis. The effects of angiotensin II (Ang Ii) were also studied in paralle l. Methods: IC were obtained by collagenase digestion of valve leaflets isolat ed from transplant recipient hearts. Changes in [Ca2+](i) were measured fro m fluorescence of the ratiometric calcium dye, fura 2. Mitogenic and collag en synthetic responses of valve IC were measured by H-3-thymidine incorpora tion (DNA synthesis) and H-3-proline incorporation assays respectively, in quiescent cells. Results: Human valve IC responded to 5-HT and Ang II with mean maximal incr eases 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 <0.05). Ang II did not stimulate IC DNA synthesis. Valve TC also res ponded to 5-HT with a maximum increase in collagen synthesis of 15.7 +/- 2. 0% by 10(-6) M 5-HT (p <0.05). Ang II provoked a more powerful collagen syn thesis response (maximum 50.5 +/- 15.1% increase by 10(-5) M Ang II; p <0.0 5). Conclusion: We have shown that 5-HT and Ang II promote the prolonged proces ses of growth and collagen synthesis in cultured human valve IC. Thus, thes e vasoactive agents may play a role in the development of heart, valve dise ase.