Wu K K
University of Texas-Houston Health Science Center, Vascular Biology Research Center 77030, USA.
J Formos Med Assoc. 1996 Sep;95(9):661-6.
Human arterial thrombotic disorders are triggered by many agents, with participation of platelets and monocytes, blood coagulation factors and vascular cells. Platelet hyperaggregability appears to be an important risk factor for these disorders. Vascular endothelium possesses several properties to defend against vascular insults and thrombotic atherosclerotic lesions. Two molecules, prostacyclin (PGI2) and nitric oxide (NO), are of particular importance. The rate-limiting step of PGI2 synthesis is cyclooxygenase (COX). Constitutive and upregulated constitutive COX (COX-1) expression and inducible COX (COX-2) expression are important in PGI2 production required for the physiologic and pathologic defense of blood vessels and blood fluidity. NO synthesis is catalyzed by endothelial nitric oxide synthase (eNOS), which can be stimulated by lipid mediators. Virus or non-virus mediated transfer of COX-1 and eNOS are accompanied by augmented PGI2 and NO synthesis, respectively. In animal angioplasty models, it has been shown that transfer of these two genes has a dramatic antithrombotic and anti-intimal hyperplastic effect. Transfers of these two enzymes may have potential therapeutic uses.
人类动脉血栓形成性疾病由多种因素引发，涉及血小板、单核细胞、血液凝固因子和血管细胞。血小板过度聚集似乎是这些疾病的一个重要危险因素。血管内皮具有多种特性以抵御血管损伤和血栓性动脉粥样硬化病变。两种分子，前列环素（PGI2）和一氧化氮（NO），尤为重要。PGI2合成的限速步骤是环氧化酶（COX）。组成型和上调的组成型COX（COX-1）表达以及诱导型COX（COX-2）表达对于血管生理和病理防御及血液流动性所需的PGI2产生很重要。NO的合成由内皮型一氧化氮合酶（eNOS）催化，其可被脂质介质刺激。COX-1和eNOS的病毒或非病毒介导转移分别伴随着PGI2和NO合成增加。在动物血管成形术模型中，已表明这两个基因的转移具有显著的抗血栓形成和抗内膜增生作用。这两种酶的转移可能具有潜在的治疗用途。
