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

越来越多的证据表明，肌细胞（MC）和非MC相互作用。（NMC）发生在心室肥厚的重塑中。我们建立了纯MC培养和MC- nmc共培养系统来检测内皮素-1 （ET-1）、心营养素-1 （CT-i）和细胞外基质蛋白、纤维连接蛋白（Fin）在相互作用中的作用。ET-1和CT-i mRNA主要在NMC中表达，在mc中表达较少，在NMC培养液中也检测到大量的ET-1和CT-i。当MCs与NMC共培养时，MCs诱导肥厚反应，如ANP/BNP的产生、细胞大小的增加和蛋白质合成的增加。ETA受体拮抗剂或抗ct -1抗体显著抑制共培养时的增生性反应，BQ1 23与抗ct -1抗体的作用本质上是相加的。这些结果清楚地表明ET-1和CT-i是主要由NMC分泌的旁分泌性肥大因子。我们还研究了Fn对mcc的影响。Fn包衣剂量依赖性地增加了蛋白质合成和ANP/BNP分泌，并伴有FAK磷酸化。RGD肽抑制了纯MC和共培养中观察到的fin诱导的MC的肥厚反应，表明Fn不仅是MC肥厚的被动参与者，而且是一个主动分子。本研究表明，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起重要作用。

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.