Role of Vascular Chemerin as a Regulator of Blood Pressure and Contributor to Cardiovascular Disease

Researchers investigated the role of chemerin as a molecular link between adipose tissue surrounding blood vessels and arterial contraction, proposing a chemerin axis in the vasculature that may connect obesity and hypertension. Using molecular and functional approaches, the team demonstrated that chemerin is synthesized and expressed in perivascular adipose tissue (PVAT) and that its primary receptor, ChemR23, is present in both the tunica media and the endothelial layer of arteries. Real-time PCR, immunohistochemistry, and Western analyses provided converging evidence for local chemerin production in PVAT and for ChemR23 expression in vascular wall components. Functionally, the ChemR23 agonist chemerin-9 produced concentration-dependent contraction in isolated rat thoracic aorta, superior mesenteric artery, and mesenteric resistance artery. Contraction responses were markedly amplified, more than doubling, when nitric oxide synthase was inhibited, the endothelium was mechanically removed, or when pre-existing tone was applied to the arteries, indicating that endothelial-derived relaxing influences and basal tone modulate chemerin's vasoconstrictive potency.

The study further employed a novel ChemR23 antagonist, CCX832, which inhibited phenylephrine- and prostaglandin F2α-induced contraction in arteries with intact PVAT, supporting the idea that endogenous chemerin released from PVAT contributes to vasoconstrictive responses. Importantly, arteries from animal models with endothelial dysfunction, such as obese or hypertensive rats, showed pronounced contraction to chemerin-9, and mesenteric arteries from obese human subjects similarly demonstrated amplified contraction, linking the chemerin axis to pathophysiological states associated with cardiovascular risk. Detailed pharmacological characterization showed that CCX832 could reverse chemerin-9-induced contraction and dampen specific agonist-induced contractions when PVAT was present, while an inactive analog, CCX826, did not, reinforcing the receptor-dependent mechanism.

Immunohistochemical images and Western blots illustrated chemerin and ChemR23 localization in arterial tissues, and quantitative analyses of receptor expression were normalized to alpha actin to support comparative conclusions across vascular beds. Collectively, these findings identify chemerin as an endogenous vasoconstrictor produced by PVAT that acts through ChemR23 expressed on vascular cells and they highlight how endothelial dysfunction and obesity amplify chemerin-mediated vascular effects. The work supports a model in which a chemerin axis contributes to increased arterial tone and potentially to elevated blood pressure in obesity and hypertension, suggesting ChemR23 and PVAT-derived chemerin as potential therapeutic targets for mitigating vascular dysfunction associated with cardiometabolic disease.