Key result
Colitis promotes pro-contractile PVAT remodeling with adipocyte hyperplasia and macrophage accumulation in mice.
Why the study?
Perivascular adipose tissue surrounds mesenteric vasculature to modulate vascular function and immune cells, but its structure and function have never been investigated in inflammatory bowel disease.
PVAT changes in colitis model should not alter IBD care; leaves open vascular-immune role for human investigation.
Inflammatory Bowel Diseases (IBDs) are associated with aberrant immune function, widespread inflammation, and altered intestinal blood flow. Perivascular adipose tissue (PVAT) surrounding the mesenteric vasculature can modulate vascular function and control the local immune cell population, but its structure and function have never been investigated in IBD. We used an IL10−/− mouse model of colitis that shares features with human IBD to test the hypothesis that IBD is associated with (1) impaired ability of PVAT to dilate mesenteric arteries and (2) changes in PVAT resident adipocyte and immune cell populations. Pressure myography and electrical field stimulation of isolated mesenteric arteries show that PVAT not only loses its anti-contractile effect but becomes pro-contractile in IBD. Quantitative immunohistochemistry and confocal imaging studies found significant adipocyte hyperplasia and increased PVAT leukocytes, particularly macrophages, in IBD. PCR arrays suggest that these changes occur alongside the altered cytokine and chemokine gene expression associated with altered NF-κB signaling. Collectively, these results show that the accumulation of macrophages in PVAT during IBD pathogenesis may lead to local inflammation, which ultimately contributes to increased arterial constriction and decreased intestinal blood flow with IBD.
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Jenkins et al. (2024) studied Inflammatory Bowel Disease. IL10-/- colitis model was evaluated on PVAT function (mesenteric artery dilation) and cellular composition. In an IL10-/- mouse model of colitis, perivascular adipose tissue became pro-contractile and exhibited adipocyte hyperplasia with increased macrophage accumulation.
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