Nishida M, Springhorn J P, Kelly R A, Smith T W
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
J Clin Invest. 1993 May;91(5):1934-41. doi: 10.1172/JCI116412.
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 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 TGF beta precursor mRNA is also markedly increased in microvascular endothelial cells in coculture and precedes the appearance of endothelin precursor transcripts. In coculture, TGF beta 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.
目前尚不清楚心室心肌中内皮细胞与肌肉细胞之间的信号传导在心脏发育过程中虽已知很重要，但在成年心脏中是否仍具有生理相关性。此外，调节局部作用的自分泌因子（如内皮素）的合成和激活的机制尚不清楚，内皮素是已知对心肌细胞收缩功能和基因表达有强大作用的细胞因子，其在心室肌中的起源细胞也不清楚。从成年大鼠心室组织分离的微血管内皮细胞不组成性表达内皮素。然而，通过与成年大鼠心室肌细胞进行异型原代培养，心脏微血管内皮细胞中前内皮素原mRNA的表达可以增加。细胞间接触，或至少紧密相邻，似乎是增加前内皮素原mRNA所必需的，因为仅用心室肌细胞条件培养基处理微血管内皮细胞单培养物时是无效的。共培养的微血管内皮细胞中TGF-β前体mRNA水平也显著增加，且先于内皮素前体转录本的出现。在共培养中，TGF-β作为一种自分泌细胞因子，增加内皮素前体mRNA并抑制微血管内皮细胞增殖速率。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与心室肌细胞之间可能也在发生动态的、相互的细胞间信号传导。
