Cominacini Luciano, Pasini Anna, Garbin Ulisse, Evangelista Stefano, Crea Attilio E G, Tagliacozzi Debora, Nava Cristina, Davoli Anna, LoCascio Vincenzo
Department of Biomedical and Surgical Sciences, Verona University, Italy.
Am J Hypertens. 2002 Oct;15(10 Pt 1):891-5. doi: 10.1016/s0895-7061(02)02995-3.
Hypertension and coronary artery disease are intimately connected. The migration of circulating monocytes into the subendothelial occurs through the expression of some adhesion molecules on endothelial cells. The nuclear factor (NF)-kappaB, a redox-sensitive element, plays a key role in adhesion molecule gene induction. In this study we have compared the effects of two different angiotensin converting enzyme (ACE) inhibitors, one possessing an active sulfhydryl group (zofenopril) and one lacking this group (enalapril) on the cellular redox state (monitored by measuring intracellular reactive oxygen species and thiol status), expression of adhesion molecules, and activation of NF-kappaB in human umbilical vein endothelial cells (HUVECs). Zofenoprilat, the active form of zofenopril, significantly and dose dependently reduced the intracellular reactive oxygen species (ROS) and superoxide formation induced by oxidized low-density lipoprotein (ox-LDL) (P <.001) and tumor necrosis factor-alpha (TNF-alpha) (P <.001). Enalaprilat, the active form of enalapril, was ineffective. Zofenoprilat but not enalaprilat also decreased the consumption of the intracellular GSH induced by ox-LDL (P <.01) and TNF-alpha (P <.01). Although zofenoprilat significantly and dose dependently reduced the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and E-selectin induced by ox-LDL (P <.01) and TNF-alpha (P <.01) on HUVECs, enalaprilat did not. Ox-LDL and TNF-alpha increased the activation of NF-kappaB and the preincubation of HUVECs with zofenoprilat, but not with enalaprilat, dose dependently reduced its activation (P <.001). The conclusion is that the sulfhydryl (SH)-containing ACE inhibitors may be useful in inhibiting foam cell formation and thus slow the development of atherosclerosis.
高血压与冠状动脉疾病密切相关。循环中的单核细胞通过内皮细胞上某些黏附分子的表达迁移至内皮下。核因子（NF）-κB是一种氧化还原敏感元件，在黏附分子基因诱导中起关键作用。在本研究中，我们比较了两种不同的血管紧张素转换酶（ACE）抑制剂，一种含有活性巯基（佐芬普利），另一种不含该基团（依那普利），对人脐静脉内皮细胞（HUVECs）细胞氧化还原状态（通过测量细胞内活性氧和巯基状态进行监测）、黏附分子表达以及NF-κB激活的影响。佐芬普利的活性形式佐芬普利拉显著且剂量依赖性地降低了氧化型低密度脂蛋白（ox-LDL）（P<.001）和肿瘤坏死因子-α（TNF-α）（P<.001）诱导的细胞内活性氧（ROS）和超氧化物形成。依那普利的活性形式依那普利拉则无效。佐芬普利拉而非依那普利拉还降低了ox-LDL（P<.01）和TNF-α（P<.01）诱导的细胞内谷胱甘肽（GSH）消耗。尽管佐芬普利拉显著且剂量依赖性地降低了ox-LDL（P<.01）和TNF-α（P<.01）诱导的人脐静脉内皮细胞上血管细胞黏附分子-1（VCAM-1）、细胞间黏附分子-1（ICAM-1）和E-选择素的表达，但依那普利拉没有。ox-LDL和TNF-α增加了NF-κB的激活，而人脐静脉内皮细胞与佐芬普利拉而非依那普利拉预孵育剂量依赖性地降低了其激活（P<.001）。结论是含巯基（SH）的ACE抑制剂可能有助于抑制泡沫细胞形成，从而减缓动脉粥样硬化的发展。
