Shear stress-induced upregulation of connexin 43 expression in endothelial cells on upstream surfaces of rat cardiac valves

Shear stress-induced upregulation of connexin 43 expression in endothelial cells on upstream surfaces of rat cardiac valves
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DOI:
10.1007/s00418-004-0717-6
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发表时间:
2004-11-01
影响因子:
2.3
通讯作者:
Shibata, Y
Shibata, Y
中科院分区:
生物学3区
文献类型:
--
作者:
Inai, T;Mancuso, MR;Shibata, Y

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差距连接蛋白(Cx)37、Cx 40和Cx 43的内皮表达在血管网络内变化。虽然以前的研究表明,剪切应力可能上调Cx43,这是不清楚,如果剪切应力影响所有的内皮连接蛋白的表达,以及在何种程度上。心脏瓣膜的上游和下游表面上的内皮细胞受到显著不同强度的剪切应力。因此,我们推断,我们可以通过比较大鼠心脏瓣膜上游和下游表面的免疫组织化学分布来确定血流动力学影响Cx 37、Cx40和Cx43表达的程度。我们发现70- 200倍更大的表达Cx43在内皮细胞的上游比下游表面。然而,Cx 37在内皮细胞的上游和下游表面上几乎相等地表达,并且在大多数血管内皮细胞中的主要连接蛋白Cx40在任一表面上均未检测到。除了Cx43表达的异质性外,上游表面的内皮细胞比相应下游表面的内皮细胞小35%至65%。这些结果表明,切应力可能会影响内皮细胞的大小和Cx43的表达,但不影响Cx 37的表达。
Endothelial expression of the gap junction proteins, connexin (Cx) 37, Cx40, and Cx43, varies within the vascular network. While previous studies suggest that shear stress may upregulate Cx43, it is not well understood if shear stress affects the expression of all endothelial connexins and to what extent. Endothelial cells on the upstream and downstream surfaces of cardiac valves are subjected to considerably different intensities of shear stress. We therefore reasoned that we could determine the extent hemodynamic forces affect the expression of Cx37, Cx40, and Cx43 by comparing their immunohistochemical distribution on the upstream and downstream surfaces of rat cardiac valves. We found 70- to 200-fold greater expression of Cx43 in the endothelial cells on the upstream than on the downstream surfaces. However, Cx37 was expressed almost equally in the endothelial cells on upstream and downstream surfaces, and Cx40, a major connexin in most vascular endothelial cells, was not detected on either surface. In addition to the heterogeneity in Cx43 expression, endothelial cells on the upstream surface were 35% to 65% smaller than those on the corresponding downstream surface. These results suggest that shear stress may affect endothelial cell size and Cx43 expression but not Cx37 expression.