Perivascular adipose tissue (PVAT) is protective and reduces the contraction of blood vessels in health. Increased immune cell infiltration and loss of the anti-contractile function of PVAT occurs with obesity and hypertension. Thus, our overall hypothesis was that T cells and macrophages in mesenteric PVAT promote release of IL-10 that causes vasorelaxation in health. In addition, we hypothesized that immunological PVAT dysfunction precedes adiposity-induced hypertension (alike in males and females). The research detailed in this dissertation provides evidence to prove or disprove our hypotheses: (1) A community of naïve, regulatory, activated and memory- type immune cells including T cells and macrophages exist in mesenteric (MRPVAT, white PVAT around mesenteric resistance arteries) and aortic (APVAT, brown PVAT around thoracic aorta) PVATs in health; (2) Mesenteric PVAT-derived IL-10 neither causes direct vasorelaxation nor reduces vasoconstriction directly or indirectly, thereby not contributing to the anti-contractile nature of PVAT in healthy mice and rats; and (3) At 10 (pre-hypertensive stage) and 17 (onset of hypertension) weeks of diet, there were greater adiposity-induced immune cell changes (CD4+ memory T cells and M2- like macrophages) in MRPVAT and APVAT from females vs males. At 24 weeks (with progression of hypertension), immune changes in PVATs began to occur in males and diminish in females.Taken together, these findings are important to know because assessing immunological PVAT function at an early stage has the potential to prevent the development of hypertension. Future studies building on this work should investigate the role of immune cells in PVATs in health and probe into the sex-differences in the immune-mechanisms contributing to vascular tone regulation in adiposity-induced hypertension.
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