Abstract
(Background) Chemerin-9 is an adipocytokine originally identified as a chemokine, especially for macrophage and dendritic cell. Chemokine (CC motif) receptor-like 2 (CCRL2), G protein-coupled receptor 1 (GPR1), and chemokine-like receptor 1 (CMKLR1) are known as chemerin receptor. Chemerin is expressed in smooth muscle and perivascular adipose tissue of mesenteric artery (MA), and induces contraction through CMKLR1. Chemerin-9, a nonapeptide derived from the C-terminal active region of chemerin, induces contraction in isolated aorta (AO). Pulmonary hypertension (PH) caused by elevated pulmonary artery (PA) pressure is lethal disease associated with right ventricular failure. We hypothesized that chemerin-9 influences pulmonary vascular resistance. Here we examined the effects of chemerin-9 on contractility of isolated PA from normal and monocrotaline (MCT)-induced PH rats.
(Methods) Isometric contraction of isolated PA, AO, or MA from normal Wistar rat and MCT (60 mg/kg, i.p., 2 weeks)-induced PH rat was measured. CMKLR1 mRNA expression in PA, AO, or MA was measured by RT-PCR.
(Results) Chemerin-9 induced contraction in normal rat PA in a concentration-dependent manner, which was potentiated by endothelium removal. Chemerin-9-induced contraction was significantly inhibited in Ca2+-free solution or in the presence of Y27632, a RhoA/ROCK inhibitor. Chemerin-9-induced contraction was the highest in PA and the lowest in AO, which seemed to be co-related with CMKLR1 mRNA expression level in the arteries. Chemerin-9-induced contraction was significantly higher in PA from MCT- induced PH rat, while CMKLR1 mRNA expression was not increased.
(Conclusion) Our study for the first time showed that chemerin-9 induces contraction perhaps via CMKLR1/Ca2+/RhoA/ROCK pathway in normal rat PA smooth muscle. In addition, the contraction is augmented in PA from MCT-induced PH rat perhaps through the activation of intracellular signals.
