Noblet Jillian N, Owen Meredith K, Goodwill Adam G, Sassoon Daniel J, Tune Johnathan D
From the Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis (J.N.N., A.G.G., D.J.S., J.D.T.); and Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill (M.K.O.).
Arterioscler Thromb Vasc Biol. 2015 Jun;35(6):1393-400. doi: 10.1161/ATVBAHA.115.305500. Epub 2015 Apr 2.
The effects of coronary perivascular adipose tissue (PVAT) on vasomotor tone are influenced by an obese phenotype and are distinct from other adipose tissue depots. The purpose of this investigation was to examine the effects of lean and obese coronary PVAT on end-effector mechanisms of coronary vasodilation and to identify potential factors involved.
Hematoxylin and eosin staining revealed similarities in coronary perivascular adipocyte size between lean and obese Ossabaw swine. Isometric tension studies of isolated coronary arteries from Ossabaw swine revealed that factors derived from lean and obese coronary PVAT attenuated vasodilation to adenosine. Lean coronary PVAT inhibited K(Ca) and KV7, but not KATP channel-mediated dilation in lean arteries. In the absence of PVAT, vasodilation to K(Ca) and KV7 channel activation was impaired in obese arteries relative to lean arteries. Obese PVAT had no effect on K(Ca) or KV7 channel-mediated dilation in obese arteries. In contrast, obese PVAT inhibited KATP channel-mediated dilation in both lean and obese arteries. The differential effects of obese versus lean PVAT were not associated with changes in either coronary KV7 or K(ATP) channel expression. Incubation with calpastatin attenuated coronary vasodilation to adenosine in lean but not in obese arteries.
These findings indicate that lean and obese coronary PVAT attenuates vasodilation via inhibitory effects on vascular smooth muscle K(+) channels and that alterations in specific factors such as calpastatin are capable of contributing to the initiation or progression of smooth muscle dysfunction in obesity.
冠状动脉血管周围脂肪组织（PVAT）对血管舒缩张力的影响受肥胖表型影响，且与其他脂肪组织储存部位不同。本研究的目的是研究瘦型和肥胖型冠状动脉PVAT对冠状动脉舒张终末效应机制的影响，并确定其中涉及的潜在因素。
苏木精-伊红染色显示，瘦型和肥胖型奥萨巴猪的冠状动脉血管周围脂肪细胞大小相似。对奥萨巴猪分离的冠状动脉进行等长张力研究发现，来自瘦型和肥胖型冠状动脉PVAT的因子减弱了对腺苷的血管舒张作用。瘦型冠状动脉PVAT抑制了瘦型动脉中K（Ca）和KV7通道，但不抑制KATP通道介导的舒张。在没有PVAT的情况下，相对于瘦型动脉，肥胖型动脉中对K（Ca）和KV7通道激活的血管舒张作用受损。肥胖型PVAT对肥胖型动脉中K（Ca）或KV7通道介导的舒张没有影响。相反，肥胖型PVAT在瘦型和肥胖型动脉中均抑制KATP通道介导的舒张。肥胖型与瘦型PVAT的不同作用与冠状动脉KV7或K（ATP）通道表达的变化无关。用钙蛋白酶抑制蛋白孵育可减弱瘦型动脉中对腺苷的冠状动脉舒张作用，但对肥胖型动脉无效。
这些发现表明，瘦型和肥胖型冠状动脉PVAT通过对血管平滑肌K（+）通道的抑制作用减弱血管舒张，并且钙蛋白酶抑制蛋白等特定因子的改变可能导致肥胖中平滑肌功能障碍的发生或进展。
