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The adipokine chemerin augments vascular reactivity to contractile stimuli via activation of the MEK-ERK1/2 pathway.

Abstract：

AIMS:Cytokines interfere with signaling pathways and mediators of vascular contraction. Endothelin-1 (ET-1) plays a major role on vascular dysfunction in conditions characterized by increased circulating levels of adipokines. In the present study we tested the hypothesis that the adipokine chemerin increases vascular contractile responses via activation of ET-1/ET-1 receptors-mediated pathways. MAIN METHODS:Male, 10-12 week-old Wistar rats were used. Endothelium-intact and endothelium-denuded aortic rings were incubated with chemerin (0.5 ng/mL or 5 ng/mL, for 1 or 24h), and isometric contraction was recorded. Protein expression was determined by Western blotting. KEY FINDINGS:Constrictor responses to phenylephrine (PE) and ET-1 were increased in vessels treated for 1h with chemerin. Chemerin incubation for 24h decreased PE contractile response whereas it increased the sensitivity to ET-1. Endothelium removal significantly potentiated chemerin effects on vascular contractile responses to PE and ET-1. Incubation with either an ERK1/2 inhibitor (PD98059) or ETA antagonist (BQ123) abolished chemerin effects on PE- and ET-1-induced vasoconstriction. Phosphorylation of MEK1/2 and ERK1/2 was significantly increased in vessels treated with chemerin for 1 and 24h. Phosphorylation of these proteins was further increased in vessels incubated with ET-1 plus chemerin. ET-1 increased MEK1/2, ERK1/2 and MKP1 protein expression to values observed in vessels treated with chemerin. SIGNIFICANCE:Chemerin increases contractile responses to PE and ET-1 via ERK1/2 activation. Our study contributes to a better understanding of the mechanisms by which the adipose tissue affects vascular function and, consequently, the vascular alterations present in obesity and related diseases.

journal_name

Life Sci

journal_title

Life sciences

authors

Lobato NS,Neves KB,Filgueira FP,Fortes ZB,Carvalho MH,Webb RC,Oliveira AM,Tostes RC

doi

10.1016/j.lfs.2012.04.013

subject

Has Abstract

pub_date

2012-10-15 00:00:00

pages

600-6

issue

13-14

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(12)00188-9

journal_volume

pub_type

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The adipokine chemerin augments vascular reactivity to contractile stimuli via activation of the MEK-ERK1/2 pathway.