title: Soluble VEGF receptor-2 is increased in sera of subjects with metabolic syndrome in association with insulin resistance.
abstract: OBJECTIVE
  Metabolic syndrome (MetS) is associated with impaired angiogenesis. Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis through binding to its specific receptor, VEGF receptor-2 (VEGFR-2), whereas the expression of VEGF and VEGFR-2 in the myocardium of insulin-resistant rats is down-regulated. Soluble VEGF receptor-1 (sVEGFR-1) and -2 (sVEGFR-2) have been reported to inhibit angiogenesis both in vitro and in vivo. However, the balance between circulating levels of VEGF and its soluble receptors, which may reflect and/or affect cardiovascular VEGF signaling, in subjects with MetS is unknown.
  
  
  RESULTS
  We carried out a cross-sectional study including 272 consecutive, apparently healthy subjects who were not receiving any drugs. Plasma levels of VEGF and serum levels of its soluble receptors were determined using enzyme-linked immunosorbent assays. VEGF and sVEGFR-1 levels did not differ between subjects with and those without MetS. However, sVEGFR-2 levels were significantly increased in MetS compared with non-MetS subjects. Stepwise regression analysis revealed that HOMA-IR was the strongest independent determinant of the sVEGFR-2 level. Accordingly, the mean sVEGFR-2 levels increased in proportion to both the accumulation of components of MetS and quartile of HOMA-IR. Interestingly, multiple regression analyses revealed that independent determinants of VEGF were the body mass index and blood pressure, whereas, in contrast, those of sVEGFR-2 were HOMA-IR and high-sensitivity C-reactive protein.
  
  
  CONCLUSIONS
  The correlation of sVEGFR-2 with insulin resistance supports the need for further investigations to define the clinical utility and predictive value of serum sVEGFR-2 levels in cardiovascular dysfunction in MetS.
authors.affiliation: Division of Translational Research, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555, Japan. hwada@kuhp.kyoto-u.ac.jp
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Wada
authors.forename: Noriko
authors.initials: N
authors.lastname: Satoh
authors.forename: Shuji
authors.initials: S
authors.lastname: Kitaoka
authors.forename: Koh
authors.initials: K
authors.lastname: Ono
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Morimoto
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Kawamura
authors.forename: Tameo
authors.initials: T
authors.lastname: Nakano
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Fujita
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Akira
authors.initials: A
authors.lastname: Shimatsu
authors.forename: Koji
authors.initials: K
authors.lastname: Hasegawa
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood*; D008875:Middle Aged; D008954:Models, Biological; D009206:Myocardium / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000097:blood; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood* / Q000378:metabolism
chemical_list: D007328:Insulin; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2