EFFECTS OF TRANSFORMING GROWTH FACTOR-BETA ON CARDIAC CELLS

转化生长因子-β此前已被认为与 心脏的胚胎发育以及心肌修复 缺血/再灌注损伤后的损伤。基于这些发现，我们 将注意力集中在转化生长因子-β对新生大鼠的直接影响上 心肌细胞。在成纤维细胞基质上培养时，细胞的搏动频率 心肌细胞被炎症介质等治疗抑制 如白介素1、肿瘤坏死因子、干扰素-γ以及 内毒素，而搏动频率是由同时 添加转化生长因子-β。我们已经证明，转化生长因子-β的能力 拮抗白介素1对心脏搏动频率的抑制作用 部分原因是它有能力抑制一氧化氮的诱导 这些肌细胞。这是第一次证明 一氧化氮的分泌与培养的新生儿心脏功能 肌细胞。转化生长因子-β拮抗一氧化氮合酶的诱导 不仅是白介素1，还有其他炎症介质。 一致认为，细胞内环核苷酸水平与一氧化氮水平平行 与已发表的一氧化氮对鸟苷酸盐活化的影响 循环酶。转化生长因子-β和白介素1作用的初步研究 对这些心肌细胞钙释放的影响表明，它们对 跳动速率可能与环状GMP对Na+/Ca2+的作用有关 交换。最后，我们证明了一氧化氮的抑制作用 对拍频的影响可以通过改变 细胞因子或培养心肌细胞的基质，证明 一氧化氮只是调节心脏跳动的几个参数之一。 肌细胞率。

Transforming growth factor-beta has previously been implicated in embryonic development of the heart as well as in repair of myocardial damage following ischemia/reperfusion injury. Based on these findings, we have focused our attention on direct effects of TGF-beta on neonatal rat cardiac myocytes. When cultured on fibroblast matrix, the beating rate of the myocytes is suppressed by treatment with inflammatory mediators such as interleukin-1, tumor necrosis factor, interferon gamma, as well as endotoxin, whereas the beating rate is maintained by the simultaneous addition of TGF-beta. We have shown that the ability of TGF-beta to antagonize the suppressive effects of interleukin-1 on the beating rate is due, in part, to its ability to suppress the induction of nitric oxide by these myocytes. This is the first demonstration of a direct link between secretion of nitric oxide and the function of cultured neonatal cardiac myocytes. TGF-beta antagonizes the induction of nitric oxide synthase by not only interleukin-1, but also by the other inflammatory mediators. Levels of cellular cyclic CMP parallel those of nitric oxide, in agreement with the published effects of nitric oxide on activation of guanylate cyclase. Preliminary studies of the effects of TGF-beta and interleukin-1 on calcium release in these myocytes suggest that some of their effects on the beating rate may involve the action of cyclic GMP on Na+/Ca2+ exchange. Finally, we show that the suppressive effects of nitric oxide on the beating rate can be overcome by altering either the set of cytokines or the matrix on which the myocytes are cultured, demonstrating that nitric oxide is but one of several parameters regulating the beating rate of the myocytes.