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20504763
Angiotensin-converting enzyme inhibition down-regulates the pro-atherogenic chemokine receptor 9 (CCR9)-chemokine ligand 25 (CCL25) axis.

J Biol Chem, 2010/7/23;285(30):23496-505.

Abd Alla J[1], Langer A, Elzahwy SS, Arman-Kalcek G, Streichert T, Quitterer U

Affiliations

PMID: 20504763DOI: 10.1074/jbc.M110.117481

Impact factor: 5.486

Abstract
Many experimental and clinical studies suggest a relationship between enhanced angiotensin II release by the angiotensin-converting enzyme (ACE) and the pathophysiology of atherosclerosis. The atherosclerosis-enhancing effects of angiotensin II are complex and incompletely understood. To identify anti-atherogenic target genes, we performed microarray gene expression profiling of the aorta during atherosclerosis prevention with the ACE inhibitor, captopril. Atherosclerosis-prone apolipoprotein E (apoE)-deficient mice were used as a model to decipher susceptible genes regulated during atherosclerosis prevention with captopril. Microarray gene expression profiling and immunohistology revealed that captopril treatment for 7 months strongly decreased the recruitment of pro-atherogenic immune cells into the aorta. Captopril-mediated inhibition of plaque-infiltrating immune cells involved down-regulation of the C-C chemokine receptor 9 (CCR9). Reduced cell migration correlated with decreased numbers of aorta-resident cells expressing the CCR9-specific chemoattractant factor, chemokine ligand 25 (CCL25). The CCL25-CCR9 axis was pro-atherogenic, because inhibition of CCR9 by RNA interference in hematopoietic progenitors of apoE-deficient mice significantly retarded the development of atherosclerosis. Analysis of coronary artery biopsy specimens of patients with coronary artery atherosclerosis undergoing bypass surgery also showed strong infiltrates of CCR9-positive cells in atherosclerotic lesions. Thus, the C-C chemokine receptor, CCR9, exerts a significant role in atherosclerosis.
MeSH terms
Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta; Apolipoproteins E; Atherosclerosis; Captopril; Chemokines, CC; Cholesterol; Coronary Artery Disease; Down-Regulation; Female; Hematopoietic Stem Cells; Humans; Macrophages; Male; Mice; Middle Aged; Monocytes; Oligonucleotide Array Sequence Analysis; Peptidyl-Dipeptidase A; Protein Transport; Receptor, Angiotensin, Type 1; Receptors, CCR; Substrate Specificity; T-Lymphocytes
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