Abstract 5511: Natural Regulatory T Cells Control Coronary Arteriolar Endothelial Dysfunction and Hypertension in Mice
Background and Purpose: Coronary arteriolar endothelial dysfunction and hypertension are the main cause for heart disease, and represent a major health problem. The cellular and molecular mechanisms that trigger this pathology are not well understood. Evidence from experimental and clinical research indicates a central role of immune cells and inflammation in cardiovascular diseases. In this study we determined that CD4+CD25+ regulatory T cells, which actively maintain immunological tolerance to self and nonself antigens, are key element in the control of blood pressure and coronary arteriolar endothelial dysfunction in angiotensin-II-dependent hypertensive mice model.
Methods and Results: Mice infused with angiotensin-II significantly increased blood pressure determined by telemetry, reduced the number of CD4+CD25+ regulatory T cells apoptosis-dependent mechanism as determined by flow cytometry, increased macrophages inflammatory cytokines release (increased local tumor necrosis factor alpha release), and induction of adhesion molecules (I-CAM and V-CAM) expression facilitating the infiltration of macrophages into coronary arterioles and heart; and induced coronary arteriolar endothelial dysfunction assessed with reduced relaxation in response to dose-response of acetylcholine using arteriograph. Interestingly, hypertensive mice injected with purified CD4+CD25+ regulatory T cells (3 times a week for two weeks) or treated with copolymer-I (which enhances the conversion of CD4+CD25− T cells to CD4+CD25+ RegTC through the induction of transcription factor Foxp3 in CD4+ T cells and Known as glatiramer acetate, novel medication for the treatment of human multiple sclerosis) significantly reduced blood pressure and macrophages inflammatory cytokines release, and improved coronary arteriolar endothelial function.
Conclusion: Our novel data strongly indicate that CD4+CD25+ regulatory T cells play a critical role in the regulation of blood pressure and coronary arteriolar endothelial function. These results provide new direction in the investigation of hypertension and coronary arteriolar disease and could lead to new therapeutic approaches that involve immune system modulation using CD4+CD25+ regulatory T cells.