Abstract 1484: Role of T- and B-Lymphocytes in Hypercholesterolemia-Induced Vasomotor Dysfunction
Hypercholesterolemia, a major risk factor for atherogenesis, is associated with inflammation and endothelial damage in large arteries. While immune cells have been implicated in the early endothelial damage caused by hypercholesterolemia, the specific population(s) of immune cells that mediate disease pathogenesis remain undefined. The objective of this study was to identify the population of lymphocytes that contributes to the endothelium impairment of large arteries that results from hypercholesterolemia. Wire myography was employed to assess vasomotor responses of aortic rings in six groups of mice: wild-type (WT) mice on a normal diet (ND), WT mice on a high cholesterol diet for 2 weeks (HC), lymphocyte-deficient Rag-1 knockout mice (Rag-1−/−) on HC, B-cell deficient mice (B-cell −/−) on HC, and mice lacking either CD4 (CD4−/−) or CD8 (CD8−/−) T lymphocytes on HC. Endothelium-independent contraction to phenylephrine did not differ between the six groups. Aortic rings from all groups exhibited comparable endothelial-independent dilation responses to sodium nitroprusside. However, HC led to an impaired endothelium-dependent vasodilation response in WT mice. This dysfunction was absent in the Rag-1−/− mice on HC. B-cell−/− and CD8−/− mice were not rescued from the impairment of acetylcholine-induced dilation caused by hypercholesterolemia. However, hypercholesterolemic CD4−/− mice were protected against the impairment of endothelium-dependent vasodilation. Our findings indicate that CD4 T-lymphocytes play a major role in mediating the impaired endothelium-dependent vasomotor responses of large arteries that accompany hypercholesterolemia.