Carbon monoxide and bile pigments: surprising mediators of vascular function
Carbon monoxide and bile pigments: surprising mediators of vascular function
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DOI：
10.1191/1358863x02vm424ra
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发表时间：
2002-08-01
影响因子：
3.5
通讯作者：
Durante, W
中科院分区：
文献类型：
--
作者：
Durante, W
血红素加氧酶 (HO) 催化血红素降解为 CO、铁和胆绿素。胆绿素随后被胆绿素还原酶代谢为胆红素。尽管长期以来被认为是血红素分解代谢的无关副产物，但最近的研究表明，CO 和胆汁色素胆绿素和胆红素可能在循环中发挥重要的生理作用。血管细胞释放的CO可通过抑制血管舒缩张力、平滑肌细胞增殖和血小板聚集来调节血流和血液流动性。 CO还可以通过直接阻断血管细胞凋亡和抑制血管壁促凋亡炎症细胞因子的释放来维持血管壁的完整性。 CO 的这些作用是通过多种途径介导的，包括激活可溶性鸟苷酸环化酶、钾通道、p38 丝裂原激活蛋白激酶或抑制细胞色素 P450。此外，胆汁色素的释放可以通过保护血管细胞免受氧化应激和抑制白细胞粘附和浸润到血管壁来维持血管稳态。在许多血管疾病中观察到 HO-1 基因表达的诱导以及随后 CO 和胆色素的释放，并且可能提供重要的适应性机制以维持血管损伤部位的稳态。因此，血管细胞通过 H2O2 催化形成 CO 和胆色素可能起到关键的内源性血管保护系统的作用。此外，将 HO-1 靶向血管壁的药理学或遗传学方法可能代表治疗血管疾病的新治疗方法。
Heme oxygenase (HO) catalyzes the degradation of heme to CO, iron, and biliverdin. Biliverdin is subsequently metabolized to bilirubin by the enzyme biliverdin reductase. Although long considered irrelevant byproducts of heme catabolism, recent studies indicate that CO and the bile pigments biliverdin and bilirubin may play an important physiological role in the circulation. The release of CO by vascular cells may modulate blood flow and blood fluidity by inhibiting vasomotor tone, smooth muscle cell proliferation, and platelet aggregation. CO may also maintain the integrity of the vessel wall by directly blocking vascular cell apoptosis and by inhibiting the release of pro-apoptotic inflammatory cytokines from the vessel wall. These effects of CO are mediated via multiple pathways, including activation of soluble guanylate cyclase, potassium channels, p38 mitogen-activated protein kinase, or inhibition of cytochrome P450. In addition, the release of bile pigments may serve to sustain vascular homeostasis by protecting vascular cells from oxidative stress and by inhibiting the adhesion and infiltration of leukocytes into the vessel wall. Induction of HO-1 gene expression and the subsequent release of CO and bile pigments are observed in numerous vascular disorders and may provide an important adaptive mechanism to preserve homeostasis at sites of vascular injury. Thus, the HO-catalyzed formation of CO and bile pigments by vascular cells may function as a critical endogenous vasoprotective system. Moreover, pharmacological or genetic approaches targeting HO-1 to the vessel wall may represent a novel therapeutic approach in treating vascular disease.