Department of Pharmacology and Toxicology, Michigan State University, MI, USA.
Department of Pharmacology and Toxicology, Michigan State University, MI, USA.
Vascul Pharmacol. 2021 Jun;138:106838. doi: 10.1016/j.vph.2021.106838. Epub 2021 Feb 1.
Perivascular adipose tissue (PVAT) is protective and reduces contraction of blood vessels in health. PVAT is composed of adipocytes, multiple types of immune cells and stromal cells. Interleukin (IL)-10, an anti-inflammatory cytokine usually produced by T cells, B cells and macrophages, was identified as one of the highly expressed (mRNA) cytokines in the mesenteric PVAT of healthy rats. One report suggested that exogenous IL-10 causes relaxation of mouse mesenteric arteries, also suggesting that IL-10 maybe a potential anti-contractile factor. Hence, we hypothesized that PVAT-derived IL-10 causes vasorelaxation and/or reduces vasoconstriction, thus contributing to the anti-contractile nature of PVAT in health. Mesenteric arteries from rats and mice expressed the receptor for IL-10 (in tunica intima and media) as determined by immunohistochemistry. Mesenteric resistance arteries for rats and superior mesenteric artery for mice were used for isometric contractility studies. Increasing concentrations [0.4-100 ng/mL] of recombinant rat/mouse (rr/mr) IL-10 or vehicle was directly added to half-maximally constricted (phenylephrine, PE) vessels (without PVAT, with endothelium). IL-10 did not cause a direct vasorelaxation. Further, the ability of rrIL-10 to cause a rightward or downward shift of a vasoconstriction-response curve was tested in the rat. The vessels were incubated with rrIL-10 [100 ng/mL or 10 ng/mL] or vehicle for 1.5 h in the tissue bath followed by a cumulative PE [10-10 M] or U46619 [10-10 M] response curve. The maximal contractions and EC values were similar in IL-10 incubated vessels vs vehicle. Thus, acute exposure of exogenous IL-10 did not reduce local vasoconstriction. To further test if endogenous IL-10 from PVAT was anti-contractile, superior mesenteric arteries from IL-10 WT and KO mice, with and without PVAT, were subjected to increasing concentrations of PE. The anti-contractile nature of PVAT was preserved with both short-term and prolonged depletion (using younger and older mice, respectively) of endogenous IL-10 in males and females. Contrary to our hypothesis, PVAT-derived IL-10 neither caused vasorelaxation nor reduced local vasoconstriction directly/indirectly. Therefore, IL-10 does not contribute to the anti-contractile nature of PVAT in healthy rodents.
血管周脂肪组织 (PVAT) 具有保护作用，可减少血管收缩。PVAT 由脂肪细胞、多种类型的免疫细胞和基质细胞组成。白细胞介素 (IL)-10 是一种抗炎细胞因子，通常由 T 细胞、B 细胞和巨噬细胞产生，被鉴定为健康大鼠肠系膜 PVAT 中高表达 (mRNA) 细胞因子之一。有一份报告表明，外源性 IL-10 可引起小鼠肠系膜动脉松弛，这也表明 IL-10 可能是一种潜在的抗收缩因子。因此，我们假设 PVAT 衍生的 IL-10 可引起血管舒张和/或减少血管收缩，从而有助于维持健康状态下 PVAT 的抗收缩特性。免疫组织化学显示，大鼠和小鼠的肠系膜动脉表达 IL-10 受体（在内膜和中膜）。用于等长收缩研究的大鼠肠系膜阻力动脉和小鼠肠系膜上动脉。将递增浓度 [0.4-100 ng/mL] 的重组大鼠/小鼠 (rr/mr) IL-10 或载体直接添加到半最大收缩（苯肾上腺素，PE）血管（无 PVAT，有内皮）中。IL-10 不会直接引起血管舒张。此外，还在大鼠中测试了 rrIL-10 引起血管收缩反应曲线右移或下移的能力。将血管在组织浴中用 rrIL-10 [100 ng/mL 或 10 ng/mL] 或载体孵育 1.5 小时，然后进行累积 PE [10-10 M] 或 U46619 [10-10 M] 反应曲线。在 IL-10 孵育的血管中，最大收缩和 EC 值与载体相似。因此，外源性 IL-10 的急性暴露并未减少局部血管收缩。为了进一步测试来自 PVAT 的内源性 IL-10 是否具有抗收缩作用，来自 IL-10 WT 和 KO 小鼠的肠系膜上动脉，有和没有 PVAT，均接受递增浓度的 PE。在雄性和雌性中，通过短期和长期（分别使用较年轻和较年长的小鼠）耗尽内源性 IL-10，保留了 PVAT 的抗收缩特性。与我们的假设相反，PVAT 衍生的 IL-10 既不能直接/间接引起血管舒张，也不能减少局部血管收缩。因此，IL-10 不会促进健康啮齿动物中 PVAT 的抗收缩特性。
