Ohta Kunio, Yachie Akihiro
Department of Pediatrics, Angiogenesis, and Vascular Development, Graduate School of Medical Science, Kanazawa, Japan.
J Endovasc Ther. 2004 Dec;11 Suppl 2:II140-50. doi: 10.1177/15266028040110S607.
The study of vascular biology has provided strong evidence for the role that free radical attack plays in the pathogenesis of cardiovascular diseases. The endothelial cell (EC) dysfunction that results from exposure to oxidative stresses, such as oxidized LDL, influences vascular cell gene expression, promoting smooth muscle cell (SMC) mitogenesis and apoptosis. These factors also play an important role in atherogenesis, which is attenuated by antioxidants. Thus, antioxidants are important to understanding the pathophysiology of cardiovascular diseases and to constructing an effective treatment strategy for these patients. Over the last decade, there has been a tremendous interest in the biology of heme oxygenase-1 (HO-1), which exhibits antioxidant effects in various forms of tissue injury. Moreover, the reaction is also the major source of carbon dioxide (CO) in the body, which is a physiologically important gaseous vasodilator that inhibits SMC proliferation. Thus, HO-1-derived products provide various mechanisms to maintain cardiovascular homeostasis. We review recent work on the cellular and molecular biological aspects of the HO/CO system in vascular pathophysiology.
血管生物学研究为自由基攻击在心血管疾病发病机制中所起的作用提供了有力证据。暴露于氧化应激(如氧化型低密度脂蛋白)导致的内皮细胞(EC)功能障碍会影响血管细胞基因表达,促进平滑肌细胞(SMC)有丝分裂和凋亡。这些因素在动脉粥样硬化形成中也起重要作用,而抗氧化剂可减轻这种作用。因此,抗氧化剂对于理解心血管疾病的病理生理学以及为这些患者构建有效的治疗策略至关重要。在过去十年中,人们对血红素加氧酶-1(HO-1)的生物学产生了浓厚兴趣,它在各种形式的组织损伤中均表现出抗氧化作用。此外,该反应还是体内二氧化碳(CO)的主要来源,CO是一种生理上重要的气态血管舒张剂,可抑制SMC增殖。因此,HO-1衍生产物提供了多种维持心血管稳态的机制。我们综述了HO/CO系统在血管病理生理学中细胞和分子生物学方面的最新研究进展。