Significance of interaction between myocytes and non-myocytes in ventricular hypertrophy.

越来越多的证据表明，心肌细胞（MC）和非MC之间的相互作用。(NMC)发生在心室肥大的重塑中。我们建立了MC纯培养和MC与NMC共培养体系，研究内皮素-1（ET-1）、心肌营养素-1（CT-1）和细胞外基质蛋白纤维连接蛋白（Fin）在MC中的相互作用，结果表明，ET-1和CT-1 mRNA主要表达于NMC，MC表达较少，在MC培养液中也检测到大量ET-1和CT-1。当MC与NMC共培养时，MC诱导肥大反应，如ANP/BNP产生，细胞大小增加和蛋白质合成增加。ETA受体拮抗剂或抗CT-1抗体可显著抑制共培养细胞的肥大反应，BQ 1 - 23和抗CT-1抗体的作用是相加的。结果表明，ET-1和CT-1是主要由NMC分泌的旁分泌性肥大因子，Fn对MC的影响是剂量依赖性的，Fn包被可促进MC的蛋白合成和ANP/BNP分泌，并伴有FAK磷酸化。RGD肽可抑制Fn诱导的MC肥大反应和共培养MC的肥大反应，提示Fn在MC肥大中不是被动参与者，而是主动分子。本研究提示MC-NMC相互作用通过旁分泌因子和细胞外基质蛋白在心室重构中发挥重要作用。

Growing evidence indicates that the interaction of myocyte (MC) and non-MC .(NMC) occurs in the remodeling of ventricular hypertrophy. We have developed the pure MC culture and MC-NMC co-culture system to examine the involvement of endothelin-1 (ET-1), cardiotrophin-1 (CT-i) and extracellular matrix proteins, fibronectin (Fin) in the interaction.ET-1 and CT-i mRNA were expressed mainly in NMC and much less expressed in MC.The substantial amount of ET-l and CT-i were also detected in the culture medium of the NMC culture. When MCs were co-cultured with NMC, MCs induce hypertrophic responses, such as ANP/BNP production, the increase in cell size and augmentation of protein synthesis. ETA receptor antagonist or anti-CT-1 antibody significantly suppressed the hypertrophic response in the co-culture, and the effect of BQ1 23 and anti CT-i Ab was additive in nature. These findings clearly indicate that ET-1 and CT-i are paracrine hypertrophic factors mainly secreted from NMC.We also examined the effect of Fn on MC.Fn-coating dose-dependently increased protein synthesis and ANP/BNP secretion, accompanied by FAK phosphorylation. The RGD peptide suppressed the Fin-induced hypertrophied response of MC on the pure MC and the hypertrophic response observed in the co-culture, suggesting that Fn is not merely passive participant but an active molecute in the MC hypertrophy. The present study indicates important roles of the MC-NMC interaction in the ventricular remodeling via paracrine factors and extracellular matrix proteins.