title: CC chemokine receptor 2 is required for macrophage infiltration and vascular hypertrophy in angiotensin II-induced hypertension.
abstract: Recent studies have identified the presence of macrophages in the arterial wall of hypertensive animals and suggested that as is the case in atherosclerosis, macrophage products may be important mediators of the adaptive response of the arterial wall. In support of this, we have previously shown that the expression of monocyte chemoattractant protein-1 is upregulated in the arteries of hypertensive animals. We hypothesized that macrophage recruitment is a critical step in the pathogenesis of hypertension. To obtain insights into this potential mechanism, we made use of mice deficient in the CC chemokine receptor 2 (CCR2), the receptor for monocyte chemoattractant protein-1. Hypertension was induced with the subcutaneous administration of angiotensin II (0.75 mg. kg(-1). d(-1)) for 7 days. Using in situ hybridization with a probe for c-fms to identify macrophages, we found that hypertension-induced macrophage infiltration of the arterial wall was virtually eliminated in CCR2-deficient mice. In addition, vascular hypertrophy was reduced by approximately 65% compared with wild-type animals. These data demonstrate that CCR2 is essential for the recruitment of macrophages into the arterial wall in the setting of hypertension. Furthermore, the decreased hypertrophic response suggests that vascular hypertrophy occurs in part as a consequence of macrophage infiltration. In angiotensin II-induced hypertension, CCR2-mediated responses are critical to the process of macrophage recruitment and vascular hypertrophy and may represent one mechanism by which at least some forms of hypertension may lead to the development of atherosclerosis.
authors.affiliation: Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: E
authors.initials: E
authors.lastname: Bush
authors.forename: N
authors.initials: N
authors.lastname: Maeda
authors.forename: W A
authors.initials: WA
authors.lastname: Kuziel
authors.forename: T C
authors.initials: TC
authors.lastname: Dawson
authors.forename: J N
authors.initials: JN
authors.lastname: Wilcox
authors.forename: H
authors.initials: H
authors.lastname: DeLeon
authors.forename: W R
authors.initials: WR
authors.lastname: Taylor
mesh_terms: D000804:Angiotensin II; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000473:pathology*; D006973:Hypertension / Q000139:chemically induced / Q000473:pathology*; D006984:Hypertrophy / Q000473:pathology; D008264:Macrophages / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000032:analysis; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000172:deficiency / Q000502:physiology*; D014657:Vasculitis / Q000209:etiology / Q000473:pathology*; D014662:Vasoconstrictor Agents
chemical_list: D015415:Biomarkers; C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D016186:Receptor, Macrophage Colony-Stimulating Factor