Chemerin influences endothelin- and serotonin-induced pulmonary artery vasoconstriction in rats

Abstract

Chemerin has been recently identified as a vasoactive adipokine implicated in blood pressure regulation. In this context, we evaluated whether chemerin could influence pulmonary vasoreactive response. Materials and methods: Vascular reactivity to chemerin and to phenylephrine, serotonin and endothelin-1 after chemerin pretreatment was evaluated in rat isolated pulmonary artery versus thoracic aorta with and without endothelium. Vasoreactivity to acetylcholine in presence of nitric oxide (NO)-synthase inhibitor (L-NAME) and to NO donor sodium nitroprusside (SNP) was evaluated in chemerin-pretreated pulmonary artery versus thoracic aorta with endothelium. Pretreatment with ODQ, a soluble guanylate cyclase inhibitor and apocynin, a ROS production inhibitor, were also tested. Arteries and lung tissue were harvested for pathobiological evaluation. Key findings: Chemerin contracted endothelium-denuded pulmonary artery, while no response was observed in arteries with endothelium. Chemerin potentiated phenylephrine-, endothelin-1-and serotonin-induced vasoconstriction, which was further enhanced by endothelium removal. Chemerin decreased acetylcholine-induced vasorelaxation in arteries with endothelium, while it did not affect SNP-induced relaxation. In presence of L-NAME, there remained a vasorelaxation in chemerin-pretreated arteries. Chemerin or ODQ alone partly decreased acetylcholine-induced vasorelaxation in pulmonary artery and thoracic aorta, while combined chemerin and ODQ incubation abolished it. Treatment with apocynin partly or totally reversed chemerin effects. In both types of arteries, chemerin reduced acetylcholine-induced NO production, as well as endothelial and inducible NO-synthase expression. Significance: Chemerin potentiates vascular responses to vasoconstrictors in pulmonary artery and thoracic aorta and, impairs acetylcholine-induced pulmonary artery vasodilatation, by mechanisms involving at least partly NO signaling and oxidative stress.

Chemerin Added to Endothelin-1 Promotes Rat Pulmonary Artery Smooth Muscle Cell Proliferation and Migration

“…Circulating serum levels of chemerin have been reported around 10 −8 mol/L in healthy lean rats and humans (Stejskal et al, 2008;Stelmanska et al, 2013) and increased in pathological conditions, such as diabetes and obesity (Zabel et al, 2005a;Lin et al, 2019). We recently showed that chemerin and its three receptors were expressed in both endothelial cells and SMCs in rat pulmonary arteries (Hanthazi et al, 2019). Here, we showed that primary cultured SMCs from rat pulmonary artery conserved in vitro the expression of chemerin and its three receptors.…”

“…RNA concentration was determined using spectrophotometry with a Nanodrop ® ND-1000 (Isogen Life Science, De Meern, Netherlands), and RNA integrity was assessed by visual inspection of GelRed (Biotium, Hayward, CA, United States)-stained agarose gels. Reverse transcription was performed with SuperScript TM II Reverse Transcriptase (Invitrogen by Thermo Fisher Scientific, Merelbeke, Belgium), according to the manufacturer’s instructions ( Hanthazi et al, 2019 ).…”

“…Result analysis was performed using an iCycler system (BioRad Laboratories, Nazareth Eke, Belgium). Relative quantification was achieved with Pfaffl method (Pfaffl, 2001) by normalization with the housekeeping genes, GAPDH and HPRT1 (Hanthazi et al, 2019). Results were expressed as relative fold increase over the mean value of relative mRNA expression of chemerin or CMKLR1 in pulmonary artery SMCs arbitrarily fixed to 1.…”

“…Chemerin, which mainly acts through the activation of CMKLR1 (Kennedy et al, 2016), was identified in the tunica intima and the tunica media of systemic (Watts et al, 2013) and pulmonary arteries (Hanthazi et al, 2019). Chemerin has been shown to promote proliferation and migration of myocytes (Yang et al, 2012) or vascular smooth muscle cells (SMCs), contributing to carotid intimal hyperplasia (Kunimoto et al, 2015).…”

Adipokines and Inflammation: Focus on Cardiovascular Diseases

“…In this line, several studies have shown that chemerin is able to promote contractility in blood vessels, including the pulmonary artery, aorta, and superior mesenteric artery in rats and the human saphenous vein [ 146 , 147 , 148 , 149 , 150 ]. It has also been demonstrated that chemerin promotes the increase of blood pressure in rats and mice [ 149 , 151 , 152 , 153 ].…”