Chemerin connects fat to arterial contraction.
Chemerin connects fat to arterial contraction.
复制标题
DOI：
10.1161/atvbaha.113.301476
复制
发表时间：
2013-06
期刊：
影响因子：
--
通讯作者：
Fink GD
中科院分区：
文献类型：
--
作者：
Watts SW;Dorrance AM;Penfold ME;Rourke JL;Sinal CJ;Seitz B;Sullivan TJ;Charvat TT;Thompson JM;Burnett R;Fink GD
Obesity and hypertension are comorbid in epidemic proportion, yet their biological connection is largely a mystery. The peptide chemerin is a candidate for connecting fat deposits around the blood vessel (perivascular adipose tissue, PVAT) to arterial contraction. We presently test the hypothesis that chemerin is expressed in PVAT and is vasoactive, supporting the existence of a chemerin axis in the vasculature. RT-PCR, immunohistochemistry and Western analyses supported the synthesis and expression of chemerin in PVAT, while the primary chemerin receptor ChemR23 was expressed both in the tunica media and endothelial layer. The ChemR23 agonist chemerin-9 caused receptor-, concentration-dependent contraction in the isolated rat thoracic aorta, superior mesenteric artery, and mesenteric resistance artery, and contraction was significantly amplified (over 100%) when nitric oxide synthase was inhibited, the endothelial cell mechanically removed or tone was placed on the arteries. The novel ChemR23 antagonist CCX832 inhibited phenylephrine- and PGF2α-induced contraction (+PVAT) suggesting that endogenous chemerin contributes to contraction. Arteries from animals with dysfunctional endothelium (obese or hypertensive) demonstrated a pronounced contraction to chemerin-9. Finally, mesenteric arteries from obese humans demonstrate amplified contraction to chemerin-9. These data support a new role for chemerin as an endogenous vasoconstrictor that operates through a receptor typically attributed to function only in immune cells.
