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The adipokine chemerin amplifies electrical field-stimulated contraction in the isolated rat superior mesenteric artery.

ABSTRACT: The adipokine chemerin causes arterial contraction and is implicated in blood pressure regulation, especially in obese subjects with elevated levels of circulating chemerin. Because chemerin is expressed in the perivascular adipose tissue (PVAT) that surrounds the sympathetic innervation of the blood vessel, we tested the hypothesis that chemerin (endogenous and exogenous) amplifies the sympathetic nervous system in mediating electrical field-stimulated (EFS) contraction. The superior mesenteric artery, with or without PVAT and with endothelium and sympathetic nerve intact, was mounted into isolated tissue baths and used for isometric contraction and stimulation. Immunohistochemistry validated a robust expression of chemerin in the PVAT surrounding the superior mesenteric artery. EFS (0.3-20 Hz) caused a frequency-dependent contraction in isolated arteries that was reduced by the chemerin receptor ChemR23 antagonist CCX832 alone (100 nM; with, but not without, PVAT), but not by the inactive congener CCX826 (100 nM). Exogenous chemerin-9 (1 ?M)-amplified EFS-induced contraction in arteries (with and without PVAT) was blocked by CCX832 and the ?-adrenergic receptor antagonist prazosin. CCX832 did not directly inhibit, nor did chemerin directly amplify, norepinephrine-induced contraction. Whole mount immunohistochemical experiments support colocalization of ChemR23 with the sympathetic nerve marker tyrosine hydroxylase in superior mesenteric PVAT and, to a lesser extent, in arteries and veins. These studies support the idea that exogenous chemerin modifies sympathetic nerve-mediated contraction through ChemR23 and that ChemR23 may be endogenously activated. This is significant because of the well-appreciated role of the sympathetic nervous system in blood pressure control.

SUBMITTER: Darios ES

PROVIDER: S-EPMC5008655 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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The adipokine chemerin amplifies electrical field-stimulated contraction in the isolated rat superior mesenteric artery.

Darios Emma S ES Winner Brittany M BM Charvat Trevor T Krasinksi Antoni A Punna Sreenivas S Watts Stephanie W SW

American journal of physiology. Heart and circulatory physiology 20160701 2

The adipokine chemerin causes arterial contraction and is implicated in blood pressure regulation, especially in obese subjects with elevated levels of circulating chemerin. Because chemerin is expressed in the perivascular adipose tissue (PVAT) that surrounds the sympathetic innervation of the blood vessel, we tested the hypothesis that chemerin (endogenous and exogenous) amplifies the sympathetic nervous system in mediating electrical field-stimulated (EFS) contraction. The superior mesenteric ...[more]

PMID: 27371688

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Project description:BackgroundAdipokine chemerin was proven to be associated with coronary artery disease (CAD), but its prognostic implications in CAD remain unclear.MethodsThis study consists of two parts, one is a basic study and the other is a clinical cohort study. First, we investigated the differential expression of six adipokines in the atherosclerotic mice model compared to mice with milder degrees of atherosclerosis and mice without atherosclerosis using microarray data. We then examined the potential of chemerin as a diagnostic and prognostic indicator in a CAD cohort. A total of 152 patients were enrolled in our study, including 77 patients with angiographically proven CAD and 75 control subjects without cardiovascular disease. Plasma adipokine chemerin levels were measured in all patients, and major adverse cardiovascular events (MACEs) were followed up, including ischemic stroke, non-fatal myocardial infarction, revascularization, and cardiovascular death.ResultsIn the aortas of atherosclerotic mice, chemerin expression was up-regulated compared to control mice. The plasma chemerin levels of CAD patients were higher than those of non-CAD patients (128.93 ± 37.06 vs. 109.85 ± 27.47 mmol/L, respectively, P < 0.001). High chemerin levels were an independent predictor of CAD (β = 2.702, 95% CI, 1.344-5.431, P = 0.001). We followed up with patients for a median duration of 5.5 years (3.9-5.6). The Kaplan-Meier curves showed that patients in the high chemerin group had a significantly higher risk of MACEs than the low chemerin group in patients with CAD (log-rank P = 0.003), not with non-CAD (Log-rank P = 0.120). Furthermore, Cox multivariate analysis revealed that high chemerin levels were an independent predictor of MACEs (HR 2.267; 95% CI, 1.139-4.515; P = 0.020). Finally, the cellular study showed that chemerin is predominantly expressed in PBMC-derived macrophages.ConclusionPlasma chemerin levels were increased in the CAD patients, and a high chemerin level increased the risk of MACEs in CAD patients.

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The adipokine chemerin amplifies electrical field-stimulated contraction in the isolated rat superior mesenteric artery.

Publications

The adipokine chemerin amplifies electrical field-stimulated contraction in the isolated rat superior mesenteric artery.

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