CCR5 deficiency is not protective in the early stages of atherogenesis in apoE knockout mice

William A. Kuziel, Tracey C. Dawson, Marlon Quinones, Edgar Garavito, George Chenaux, Seema S. Ahuja, Robert L. Reddick, Nobuyo Maeda

Research output: Contribution to journalArticle

135 Scopus citations

Abstract

The accumulation of macrophages and T lymphocytes in vessel walls is a hallmark of atherogenesis. It has recently been demonstrated in mouse models of atherosclerosis that full disease potential is dependent on several regulators of leukocyte trafficking, including the chemokine monocyte chemotactic protein 1 (MCP-1) and the chemokine receptors CCR2 and CXCR2. A possible role for the chemokine receptor CCR5 in atherogenesis has been suggested by CCR5 expression on macrophages, T cells, coronary endothelial cells and aortic smooth muscle cells and by the presence of CCR5 ligands in atherosclerotic plaques. Moreover, individuals who are naturally deficient in CCR5 were reported to be at reduced risk for severe coronary artery disease (CAD) and early myocardial infarction (MI). To investigate whether CCR5 is pro-atherogenic in mice, we generated CCR5-deficient mice and crossed them with atherosclerosis-prone apoE-deficient mice. Although CCR5-deficient mice exhibit defects in induced macrophage trafficking, mean atherosclerotic lesion area did not differ significantly between apoE-deficient mice and apoE/CCR5-deficient mice after 16 weeks on a diet of normal chow. Ribonuclease protection assays (RPA) on RNA isolated from plaques from both apoE-deficient and apoE/CCR5-deficient animals showed strong signals for the macrophage marker F4/80 but no evidence for expression of prominent markers of T and B lymphocytes. These results indicate that the early stages of plaque formation in this model of lipid-mediated atherogenesis do not depend on CCR5.

Original languageEnglish (US)
Pages (from-to)25-32
Number of pages8
JournalAtherosclerosis
Volume167
Issue number1
DOIs
StatePublished - Mar 1 2003

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Keywords

  • Atherosclerosis
  • Chemokine receptors
  • Inflammation
  • Knockout mice
  • Macrophages

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Kuziel, W. A., Dawson, T. C., Quinones, M., Garavito, E., Chenaux, G., Ahuja, S. S., Reddick, R. L., & Maeda, N. (2003). CCR5 deficiency is not protective in the early stages of atherogenesis in apoE knockout mice. Atherosclerosis, 167(1), 25-32. https://doi.org/10.1016/S0021-9150(02)00382-9