Enalapril attenuates angiotensin II-induced atherosclerosis and vascular inflammation

Valdeci Da Cunha, Doris M. Tham, Baby Martin-McNulty, Gary Deng, Jerrick J. Ho, Dennis W Wilson, John C Rutledge, Ronald Vergona, Mark E. Sullivan, Yi Xin Wang

Research output: Contribution to journalArticle

135 Scopus citations

Abstract

Angiotensin converting enzyme (ACE) inhibitors prevent a wide variety of key events underlying atherogenesis. Whether these actions depend solely on reduction of angiotensin II (Ang II) 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 II in apolipoprotein E-deficient (apoE-KO) mice. Subcutaneous infusion of Ang II (1.44 mg/(kg day)) for 4 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 macrophage-colony stimulating factor (M-CSF) was up-regulated in the aortas of Ang 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 II-induced over-expression of adhesion molecules and chemokines in the aorta, enalapril up-regulated the expression of peroxisome proliferator-activated receptors (PPARs)-α and -γ, potential anti-inflammatory transcription factors. In the aortic arch, a lesion-prone site, the co-treatment 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 Ang II-independent mechanisms in the antiatherogenic and anti-inflammatory effects of ACE inhibitors.

Original languageEnglish (US)
Pages (from-to)9-17
Number of pages9
JournalAtherosclerosis
Volume178
Issue number1
DOIs
StatePublished - Jan 2005

Keywords

  • ACE inhibitor
  • Angiotensin
  • Atherosclerosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Da Cunha, V., Tham, D. M., Martin-McNulty, B., Deng, G., Ho, J. J., Wilson, D. W., Rutledge, J. C., Vergona, R., Sullivan, M. E., & Wang, Y. X. (2005). Enalapril attenuates angiotensin II-induced atherosclerosis and vascular inflammation. Atherosclerosis, 178(1), 9-17. https://doi.org/10.1016/j.atherosclerosis.2004.08.023