Enalapril attenuates angiotensin II-induced atherosclerosis and vascular inflammation

Angiotensin converting enzyme (ACE) inhibitors prevent a wide variety of key events underlying atherogenesis. Whether these actions depend solely on reduction of angiotensin 11 (Ang 11) generation is still to be determined. This study was undertaken to determine whether enalapril, an ACE inhibitor, prevents atherosclerosis and vascular inflammation induced by Ang H in apolipoprotein E-deficient (apoE-KO) mice. Subcutaneous infusion of Ang 11 (1.44 mg/kg day)) for4 weeks increased blood pressure and accelerated atherosclerosis development in the carotid arteries. The expression of the endothelial adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM- 1) and vascular cell adhesion molecule-1 (VCAM-1), as well as the chemokines monocyte chemotactic protein-1 (,MCP-1) and macrophave-colony-stimulating factor (M-CSF) was up-regulated in the aortas of Ana II-treated mice. Enalapril co-treatment (25 mg/(kg day. in drinking water) prevented the development of atherosclerosis without affecting blood pressure or circulating cholesterol. In addition to preventing the Ang H-induced over-expression of adhesion molecules and chemokines in the aorta, enalapril up-regulated the expression of peroxisome proliferator-activated receptors (PPARs)-alpha and -gamma, potential anti-inflammatory transcription factors. In the aortic arch, a lesion-prone site. the co-treatmemt with enalapril reduced the percentage of arterial wall occupied by macrophages and foam cells, medial sclerosis and elastin reduplication. Together. these data suggest an important role for Ana II-independent mechanisms in the antiatherogenic and anti-inflammatory effects of ACE inhibitors. (C) 2004 Elsevier Ireland Ltd. All rights reserved.