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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1998.)
© 2007 American Heart Association, Inc.

Vascular Biology

T-Cell–Derived Interferon- Contributes to Arteriolar Dysfunction During Acute Hypercholesterolemia

Karen Y. Stokes; Shelly Gurwara; D. Neil Granger

From the Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, La.

Correspondence to D. Neil Granger, PhD, Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 E Kings Highway, Shreveport, LA 71130-3932. E-mail dgrang{at}lsuhsc.edu

Objectives— T-lymphocytes and interferon- (IFN-) contribute to leukocyte recruitment in postcapillary venules during hypercholesterolemia. Our objectives were to determine whether: (1) T-lymphocytes are the source of this IFN-, and (2) whether T-cell–derived IFN- also mediates the accompanying arteriolar dysfunction and platelet adhesion.

Methods and Results— Intravital videomicroscopy was used to quantify arteriolar responses to acetylcholine, and leukocyte and platelet adhesion in postcapillary venules of wild-type (WT), immunodeficient (SCID), and IFN-^–/– mice on a normal (ND) or high-cholesterol (HC) diet. Acetylcholine-induced arteriolar dilation was impaired in WT-HC, compared with WT-ND. This endothelial dysfunction was absent in SCID-HC or IFN-^–/–-HC mice. Vasodilation was impaired by transfer of WT, but not IFN-^–/–, T-cells to these immunodeficient mice. WT-HC mice exhibited elevated leukocyte and platelet adhesion in venules, versus WT-ND. This blood cell recruitment was attenuated to ND levels in SCID-HC and IFN-^–/–-HC mice, but restored to WT-HC levels by transfer of WT, but not IFN-^–/–, T-lymphocytes.

Conclusions— These data reveal a novel role of T-lymphocyte–derived IFN- in the development of endothelial dysfunction in arterioles during hypercholesterolemia and extend our previous observations that IFN- mediates both inflammatory and thrombogenic responses to hypercholesterolemia in postcapillary venules.

IFN- mediates leukocyte adhesion in venules during hypercholesterolemia. This study determines whether this IFN- is derived from T-cells and whether it mediates the accompanying platelet adhesion and arteriolar dysfunction. Our findings reveal an indirect role for T-lymphocyte–derived IFN- in impaired arteriolar vasodilation, and venular inflammatory and thrombogenic responses to hypercholesterolemia.

Key Words: T-lymphocytes • interferon- • hypercholesterolemia • endothelial dysfunction • platelets

This article has been cited by other articles:

				K. Y. Stokes, L. Calahan, C. M. Hamric, J. M. Russell, and D. N. Granger CD40/CD40L contributes to hypercholesterolemia-induced microvascular inflammation Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H689 - H697. [Abstract] [Full Text] [PDF]

				R. M. Wolfort, K. Y. Stokes, and D. N. Granger CD4+ T lymphocytes mediate hypercholesterolemia-induced endothelial dysfunction via a NAD(P)H oxidase-dependent mechanism Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2619 - H2626. [Abstract] [Full Text] [PDF]