title: Natural regulatory T cells control coronary arteriolar endothelial dysfunction in hypertensive mice.
abstract: Coronary artery disease in patients with hypertension is increasing worldwide and leads to severe cardiovascular complications. The cellular and molecular mechanisms that underlie this pathologic condition are not well understood. Experimental and clinical research indicates that immune cells and inflammation play a central role in the pathogenesis of cardiovascular diseases. Recently, it has been reported that CD4(+)CD25(+) regulatory T cells (Tregs) regulate heart fibrosis in hypertension. In this study, we determined the role of Tregs in coronary arteriolar endothelial dysfunction in angiotensin II-dependent hypertensive mice. Mice infused with angiotensin II had significantly increased blood pressure, as determined using telemetry, and apoptotic Treg numbers, as measured using flow cytometry. The mice displayed inflammation, assessed by macrophage activation/infiltration into coronary arterioles and the heart, and increased local tumor necrosis factor-α release, which participates in reduced coronary arteriolar endothelial-dependent relaxation in response to acetylcholine using an arteriograph. Hypertensive mice injected with Tregs isolated from control mice had significantly reduced macrophage activation and infiltration, reduced tumor necrosis factor-α release, and improved coronary arteriolar endothelium-dependent relaxation. Our novel data indicate that Tregs are important in the development of coronary arteriolar endothelial dysfunction in hypertension. These results suggest a new direction in the investigation of vascular disease in hypertension and could lead to a therapeutic strategy that involves immune system modulation using Tregs.
authors.affiliation: Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University, New Orleans, Louisiana 70112, USA. kmatroug@tulane.edu
authors.forename: Khalid
authors.initials: K
authors.lastname: Matrougui
authors.forename: Zakaria
authors.initials: Z
authors.lastname: Abd Elmageed
authors.forename: Abd Elmageed
authors.initials: AE
authors.lastname: Zakaria
authors.forename: Modar
authors.initials: M
authors.lastname: Kassan
authors.forename: Sookyoung
authors.initials: S
authors.lastname: Choi
authors.forename: Devika
authors.initials: D
authors.lastname: Nair
authors.forename: Romer A
authors.initials: RA
authors.lastname: Gonzalez-Villalobos
authors.forename: Aziz A
authors.initials: AA
authors.lastname: Chentoufi
authors.forename: Philip
authors.initials: P
authors.lastname: Kadowitz
authors.forename: Souad
authors.initials: S
authors.lastname: Belmadani
authors.forename: Megan
authors.initials: M
authors.lastname: Partyka
mesh_terms: D000818:Animals; D001160:Arterioles / Q000276:immunology / Q000503:physiopathology; D003331:Coronary Vessels / Q000276:immunology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000276:immunology / Q000503:physiopathology*; D006973:Hypertension / Q000276:immunology / Q000503:physiopathology*; D018655:Lymphocyte Count; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*