Abstract
BackgroundChemerin, a novel adipokine, plays a role in the inflammation status of vascular endothelial cells. Hypoxia causes endothelial-cell proliferation, migration, and angiogenesis. This study was aimed at evaluating the protein and mRNA expression of chemerin after exposure of human coronary artery endothelial cells (HCAECs) to hypoxia.Methods and ResultsCultured HCAECs underwent hypoxia for different time points. Chemerin protein levels increased after 4 h of hypoxia at 2.5% O2, with a peak of expression of tumor necrosis factor-alpha (TNF-alpha) at 1 h. Both hypoxia and exogenously added TNF-alpha during normoxia stimulated chemerin expression, whereas an ERK inhibitor (PD98059), ERK small interfering RNA (siRNA), or an anti-TNF-alpha antibody attenuated the chemerin upregulation induced by hypoxia. A gel shift assay indicated that hypoxia induced an increase in DNA-protein binding between the chemerin promoter and transcription factor SP1. A luciferase assay confirmed an increase in transcriptional activity of SP1 on the chemerin promoter during hypoxia. Hypoxia significantly increased the tube formation and migration of HCAECs, whereas PD98059, the anti-TNF-alpha antibody, and chemerin siRNA each attenuated these effects.ConclusionHypoxia activates chemerin expression in cultured HCAECs. Hypoxia-induced chemerin expression is mediated by TNF-alpha and at least in part by the ERK pathway. Chemerin increases early processes of angiogenesis by HCAECs after hypoxic treatment.
Highlights
Adipose tissue acts as an endocrine organ that produces and secretes multiple immunomodulatory proteins known as adipokines [1]
Both hypoxia and exogenously added TNF-alpha during normoxia stimulated chemerin expression, whereas an ERK inhibitor (PD98059), ERK small interfering RNA, or an anti-TNF-alpha antibody attenuated the chemerin upregulation induced by hypoxia
Chemerin protein expression was notably increased when human coronary artery endothelial cells (HCAECs) were subjected to 2.5% O2 hypoxia for 4 h as compared to other conditions
Summary
Adipose tissue acts as an endocrine organ that produces and secretes multiple immunomodulatory proteins known as adipokines [1]. The number of known members of the adipokine family continues to grow, including leptin, adiponectin, apelin, interleukin 6 (IL-6), and chemerin [2] Some of these adipokines are pleiotropic cytokines, which participate in inflammation and immune regulation [3]. Chemokine like receptor 1 (CMKLR1), a Gi protein-coupled chemerin receptor is highly expressed in vascular endothelial cells and is regulated by several proinflammatory cytokines, including tumor necrosis factor-alpha (TNFalpha) and IL-6 [12]. Taken together, these data suggest that chemerin may be an independent adipocytokine marker of the inflammatory state of vascular endothelial cells and cardiovascular disease [13]
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