Endothelial cell expression of vasoconstrictors and growth factors is regulated by smooth muscle cell-derived carbon monoxide
Endothelial cell expression of vasoconstrictors and growth factors is regulated by smooth muscle cell-derived carbon monoxide
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DOI：
10.1172/jci118334
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发表时间：
1995-12-01
影响因子：
15.9
通讯作者：
Kourembanas, S
中科院分区：
文献类型：
--
作者：
Morita, T;Kourembanas, S
一氧化碳是由血红素加氧酶-1（HO-1）在血管平滑肌细胞（VSMC）中产生的。一氧化碳增加环鸟苷酸水平的VSM，然而，其可能的额外的作用，在脉管系统尚未检查，我们报告的产品HO，从VSMC释放和血红蛋白抑制，对内皮细胞的旁分泌作用：它增加内皮细胞环鸟苷酸含量，并减少有丝分裂原，内皮素-1（ET-1）和血小板衍生生长因子-E（PDGF-B）的表达。该产品具有CO的特性，在缺氧条件下其产量增加7倍，VSMC衍生的CO引起内皮细胞cGMP增加4倍，此外，它抑制缺氧诱导的ET-1和PDGP-B基因mRNA水平的增加，HO抑制剂和CO清除剂血红蛋白阻止cGMP的升高，并恢复这些基因的缺氧反应，CO抑制ET-1和PDGF-B mRNA的表达，可导致内皮源性丝裂原的产生减少，进而抑制VSMC的增殖。这些结果表明，VSMC源性CO在调节缺氧时血管壁细胞间相互作用和细胞增殖中具有重要的生理作用。
CO is produced in vascular smooth muscle cells (VSMC) by heme oxygenase-1 (HO-1). CO increases cGMP levels in VSM; however, its possible additional roles in the vasculature have not been examined, We report that a product of HO, released from VSMC and inhibited by hemoglobin, has paracrine effects on endothelial cells: it increases endothelial cGMP content and decreases the expression of the mitogens, endothelin-1 (ET-1) and platelet-derived growth factor-E (PDGF-B). This product has the characteristics of CO, and its production is increased sevenfold under hypoxia, The VSMC-derived CO caused a fourfold rise in endothelial cell cGMP, In addition, it inhibited the hypoxia-induced increases in mRNA levels of the ET-1 and PDGP-B genes, Inhibitors of HO, and hemoglobin, a scavenger of CO, prevented the rise in cGMP and also restored the hypoxic response of these genes, The inhibition of ET-1 and PDGF-B mRNA by CO resulted in decreased production of these endothelial-derived mitogens, and in turn, inhibition of VSMC proliferation, These findings suggest an important physiologic role for VSMC-derived CO in modulating cell-cell interaction and cell proliferation in the vessel wall during hypoxia.