CELL-CELL SIGNALING BETWEEN ADULT-RAT VENTRICULAR MYOCYTES AND CARDIAC MICROVASCULAR ENDOTHELIAL-CELLS IN HETEROTYPIC PRIMARY CULTURE
CELL-CELL SIGNALING BETWEEN ADULT-RAT VENTRICULAR MYOCYTES AND CARDIAC MICROVASCULAR ENDOTHELIAL-CELLS IN HETEROTYPIC PRIMARY CULTURE
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DOI：
10.1172/jci116412
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发表时间：
1993-05-01
影响因子：
15.9
通讯作者：
SMITH, TW
中科院分区：
文献类型：
--
作者：
NISHIDA, M;SPRINGHORN, JP;SMITH, TW
目前尚不清楚已知在心脏发育过程中重要的心肌内皮细胞和肌肉细胞之间的信号在成人心脏中是否仍具有生理相关性。此外，调节局部作用的类血管紧张素的合成和激活的机制尚不清楚，就像它们在心室肌中的起源细胞一样。内皮素是已知对心肌细胞的收缩功能和基因表达具有强大影响的细胞因子。分离的成年大鼠心肌微血管内皮细胞不表达内皮素。然而，与成年大鼠心肌细胞异型原代培养可增加心脏微血管内皮细胞内前内皮素原mRNA的表达。细胞与细胞的接触，或至少是紧密的结合，似乎是增加前内皮素mRNA所必需的，因为仅由心室肌细胞条件的培养液应用于微血管内皮细胞的单一培养是无效的。微血管内皮细胞在共培养过程中，TGFβ前体mRNA水平也明显升高，并先于内皮素前体转录本的出现。在共培养中，TGFβ作为一种自分泌细胞因子，增加内皮素前体mRNA，抑制微血管内皮细胞的增殖。异型原代培养中内皮细胞表型的这种调节表明，体内微血管内皮细胞和心室肌细胞之间也可能发生动态的、相互的细胞-细胞信号转导。
It is unclear whether signaling between endothelial cells and muscle cells within ventricular myocardium, known to be important during cardiac development, remains physiologically relevant in the adult heart. Also, the mechanisms regulating the synthesis and activation of locally acting autacoids such as endothelins, cytokines known to have potent effects on contractile function and gene expression in cardiac myocytes, are unknown, as are their cells of origin within ventricular muscle. Microvascular endothelial cells isolated from ventricular tissue of adult rats do not express endothelins constitutively. However, the appearance of preproendothelin MRNA can be increased in cardiac microvascular endothelial cells by heterotypic primary culture with adult rat ventricular myocytes. Cell-cell contact, or at least close apposition, appears to be necessary to increase preproendothelin mRNA, as medium conditioned by ventricular myocytes alone was ineffective when applied to monocultures of microvascular endothelial cells. The level of TGFbeta precursor mRNA is also markedly increased in microvascular endothelial cells in coculture and precedes the appearance of endothelin precursor transcripts. In coculture, TGFbeta acts as an autocrine cytokine, increasing endothelin precursor mRNA and inhibiting the rate of microvascular endothelial cell proliferation. This regulation of endothelial cell phenotype in heterotypic primary cultures suggests that dynamic, reciprocal cell-cell signaling may also be occurring between microvascular endothelium and ventricular myocytes in vivo.