Extracellular acidosis induces heme oxygenase-1 expression in vascular smooth muscle cells
Extracellular acidosis induces heme oxygenase-1 expression in vascular smooth muscle cells
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DOI：
10.1152/ajpheart.00937.2004
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发表时间：
2005-06-01
影响因子：
4.8
通讯作者：
Kourembanas, S
中科院分区：
文献类型：
--
作者：
Christou, H;Bailey, N;Kourembanas, S
细胞外酸中毒(EA)对血管内稳态有深远的影响，包括血管床层特有的血管张力改变。在包括血管内皮细胞在内的多种细胞中，已观察到电针对基因表达的调节。电针是否调节血管平滑肌细胞的基因表达尚不清楚。血红素氧合酶(HO)-1在血管细胞中表达，其表达受热、辐射和低氧等细胞应激因素的调节。血管平滑肌细胞HO-1表达增加导致CO及其第二信使cGMP的产生增加，这是血管张力和旁分泌相互作用的重要调节因素。我们检测了电针是否调节VSMC中HO-1的表达。与生理pH(pH 7.4)相比，酸性(pH 6.8)培养的VSMC HO-1mRNA和HO-1蛋白表达显著增加。酸性诱导HO-1的表达具有时间依赖性，既涉及HO-1基因的转录激活，也涉及HO-1mRNA的稳定性增强。一氧化氮似乎不是这一反应的中介。我们的结论是，HO-1在转录和转录后均被电针上调。这种诱导是时间依赖的和可逆的。我们推测，电针作为VSMCs的重要组织和细胞应激源，可能会引起基因表达模式的变化，从而有助于维持或破坏血管内环境的稳定。
Extracellular acidosis (EA) has profound effects on vascular homeostasis, including vascular bed-specific alterations in vascular tone. Regulation of gene expression by EA has been observed in a variety of cells including vascular endothelial cells. Whether EA regulates gene expression in vascular smooth muscle cells (VSMCs) is not known. Heme oxygenase (HO)-1 is expressed in vascular cells, and its expression is regulated by cellular stressors such as heat, radiation, and hypoxia. Increased HO-1 expression in VSMCs leads to increased production of CO and its second messenger cGMP, which are important regulators of vascular tone and paracrine interactions in the vasculature. We examined whether EA regulates the expression of HO-1 in VSMCs. Exposure of VSMCs to acidic medium (pH 6.8) significantly increased HO-1 mRNA and protein compared with exposure to medium of physiological pH (pH 7.4). The acidic induction of HO-1 expression was time dependent and involved both transcriptional activation of the HO-1 gene and enhanced stability of HO-1 mRNA. Nitric oxide did not appear to mediate this response. We conclude that HO-1 is transcriptionally and posttranscriptionally upregulated by EA in VSMCs. This induction is time dependent and reversible. We speculate that EA, as an important tissue and cellular stressor for VSMCs, may elicit changes in gene expression patterns that contribute to the maintenance or disruption of vascular homeostasis.