Chemerin-9-induced contraction was enhanced through the upregulation of smooth muscle chemokine-like receptor 1 in isolated pulmonary artery of pulmonary arterial hypertensive rats.

Abstract

Chemerin is an adipocytokine having cardiovascular effects. Chemokine-like receptor 1 (CMKLR1) and chemokine (CC motif) receptor-like 2 (CCRL2) are chemerin receptors. Chemerin-9, an active fragment, causes contraction via smooth muscle CMKLR1 in isolated blood vessels. Pulmonary arterial hypertension (PAH) is a fatal disease resulting ultimately in right heart failure. To test the hypothesis that chemerin affects pulmonary artery (PA) resistance, we examined the effects of chemerin-9 on contractility of isolated PA from PAH rats. Wistar rats were injected with monocrotaline (MCT) for 2weeks to make PAH rats (MCT rats). Control (Cont) rats received a saline injection. Chemerin-9-induced contraction of isolated intrapulmonary artery (IPA) from left lung was isometrically measured. Protein expression of CMKLR1 and CCRL2 in isolated left lung was determined by Western blotting. Localization of CMKLR1 in IPA of left lung was examined immunohistochemically. Chemerin-9-induced contraction was significantly enhanced in IPA from MCT compared with Cont rats. Protein expression of CMKLR1 was significantly elevated in isolated left lung from MCT compared with Cont rats, while protein expression of CCRL2, a decoy receptor, was significantly decreased. CMKLR1 was localized mainly in endothelium of IPA in Cont rats. The CMKLR1 expression was significantly decreased in endothelium of IPA in MCT rats, while it was significantly elevated in smooth muscle. The present study for the first time demonstrated that the enhanced chemerin-9-induced contraction of isolated IPA from MCT rats was at least partly caused by the increase of CMKLR1 in smooth muscle.