Zofenopril inhibits the expression of adhesion molecules on endothelial cells by reducing reactive oxygen species

• Published in: American journal of hypertension 2002-10, Vol.15 (10), p.891-895
• Main Authors: Cominacini, Luciano, Pasini, Anna Fratta, Garbin, Ulisse, Evangelista, Stefano, Crea, Attilio E.G, Tagliacozzi, Debora, Nava, Cristina, Davoli, Anna, LoCascio, Vincenzo
• Format: Article
• Language: English
• Subjects: ACE inhibitors; Angiotensin-Converting Enzyme Inhibitors - pharmacology; antioxidants; Atherosclerosis; Biological and medical sciences; Captopril - analogs & derivatives; Captopril - pharmacology; Cardiovascular system; Cell Adhesion Molecules - metabolism; Cells, Cultured; E-Selectin - metabolism; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Glutathione - metabolism; Humans; hypertension; Intercellular Adhesion Molecule-1 - metabolism; Lipoproteins, LDL - metabolism; Medical sciences; NF-kappa B - metabolism; Pharmacology. Drug treatments; reactive oxygen species; Reactive Oxygen Species - metabolism; Superoxides - metabolism; Umbilical Veins - cytology; Vascular Cell Adhesion Molecule-1 - metabolism; Vasodilator agents. Cerebral vasodilators
• ISSN: 0895-7061; 1879-1905; 1941-7225
• 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)-κB, 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-κB 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-α (TNF-α) (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-α (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-α (P < .01) on HUVECs, enalaprilat did not. Ox-LDL and TNF-α increased the activation of NF-κB 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.