Chemerin, a novel adipokine in the regulation of angiogenesis.
BACKGROUND
Chemerin is a new adipokine associated with obesity and the metabolic syndrome. Gene expression levels of chemerin were elevated in the adipose depots of obese compared with lean animals and was markedly elevated during differentiation of fibroblasts into mature adipocytes.


OBJECTIVE
The objective of the study was to identify factors that affect the regulation and potential function of chemerin using a genetics approach.


METHODS
Plasma chemerin levels were measured in subjects from the San Antonio Family Heart Study, a large family-based genetic epidemiological study including 1354 Mexican-American individuals. Individuals were randomly sampled without regard to phenotype or disease status.


METHODS
A genome-wide association analysis using 542,944 single-nucleotide polymorphisms in a subset of 523 of the same subjects was undertaken. The effect of chemerin on angiogenesis was measured using human endothelial cells and interstitial cells in coculture in a specially formulated medium.


RESULTS
Serum chemerin levels were found to be highly heritable (h(2) = 0.25; P = 1.4 x 10(-9)). The single-nucleotide polymorphism showing strongest evidence of association (rs347344; P = 1.4 x 10(-6)) was located within the gene encoding epithelial growth factor-like repeats and discoidin I-like domains 3, which has a known role in angiogenesis. Functional angiogenesis assays in human endothelial cells confirmed that chemerin significantly mediated the formation of blood vessels to a similar extent as vascular endothelial growth factor.


CONCLUSIONS
Here we demonstrate for the first time that plasma chemerin levels are significantly heritable and identified a novel role for chemerin as a stimulator of angiogenesis.
Metabolic Research Unit, Deakin University, Geelong 3217, Australia.
Kiymet
K
Bozaoglu
Joanne E
JE
Curran
Claire J
CJ
Stocker
Mohamed S
MS
Zaibi
David
D
Segal
Nicky
N
Konstantopoulos
Shona
S
Morrison
Melanie
M
Carless
Thomas D
TD
Dyer
Shelley A
SA
Cole
Harald H H
HH
Goring
Eric K
EK
Moses
Ken
K
Walder
Michael A
MA
Cawthorne
John
J
Blangero
Jeremy B M
JB
Jowett
D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics; D018925:Chemokines / Q000097:blood / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006706:Homeostasis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D017058:Mexican Americans; D018919:Neovascularization, Physiologic / Q000235:genetics; D009765:Obesity / Q000235:genetics; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013498:Suramin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C478630:RARRES2 protein, human; D042461:Vascular Endothelial Growth Factor A; D013498:Suramin; D004247:DNA