VEGF-C and soluble VEGF receptor-3 are increased in sera of subjects with metabolic syndrome in association with soluble VEGF receptor-2

VEGF-C and soluble VEGF receptor-3 are increased in sera of subjects with metabolic syndrome in association with soluble VEGF receptor-2

Shuichi Ura1, Hiromichi Wada1, Shuji Kitaoka1, Noriko Satoh-Asahara1, Tomohide Takaya1, Rieko Takanabe-Mori1, Masaharu Akao1, Mitsuru Abe1, Tatsuya Morimoto2, Masatoshi Fujita3, Akira Shimatsu1, Koji Hasegawa1.

  1. Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
  2. School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
  3. Graduate School of Medicine, Kyoto University, Kyoto, Japan.

The 6th China-Japan Cardiovascular Forum (Beijing, China), 2010/10/16 (Poster).

Abstract

Background: Vascular endothelial growth factor-C (VEGF-C) plays a key role in lymphangiogenesis through binding to VEGF receptor-3 (VEGFR-3). A recent report demonstrated that naturally occurring soluble VEGFR-2 (sVEGFR-2) acts as a VEGF-C antagonist, while we reported that serum sVEGFR-2 levels are increased in patients with metabolic syndrome (MetS). However, circulating levels of VEGF-C and soluble VEGFR-3 (sVEGFR-3) in patients with MetS are unknown.

Methods and Resuts: We carried out a cross sectional study involving 239 consecutive, apparently healthy subjects not receiving any drugs. They were divided into 42 MetS (mean age: 47±8 (SD) years, 35 men and 7 women) and 197 non-MetS (45±9 years, 128 men and 69 women) subjects according to the NCEP-ATP criteria. Circulating levels of VEGF-A and those of soluble VEGF receptor-1 did not differ between subjects with and those without MetS. However, levels of VEGF-C and sVEGFR-3 were significantly increased in MetS compared with non-MetS subjects (P = 0.01 and P = 0.0004, respectively). Both the mean VEGF-C and sVEGFR-3 levels increased in proportion to the accumulation of components of MetS. After adjusting for age and gender, VEGF-C levels were significantly correlated with the body mass index (BMI), systolic (SBP) and diastolic (DBP) blood pressures, and triglycerides (TG), low-density-lipoprotein cholesterol, non-high-density-lipoprotein cholesterol, and sVEGFR-2 levels, whereas sVEGFR-3 was correlated with SBP, DBP, and sVEGFR-2. Stepwise regression analyses revealed that TG, sVEGFR-2, and DBP were independent determinants of VEGF-C, and that sVEGFR-2 was an independent determinant of sVEGFR-3. Interestingly, multiple regression analyses, including data on the BMI, DBP, and TG, revealed that TG and the DBP were independent determinants of VEGF-C, in marked contrast to the fact that the BMI was an independent determinant of VEGF-A, suggesting that VEGF-C is more closely associated with atherosclerotic risk factors than VEGF-A.

Conclusions: Serum levels of VEGF-C/VEGFR-3 were increased in MetS in association with sVEGFR-2, an endogenous antagonist of VEGF-C. Further investigations are required to define the clinical utility of VEGF-C/sVEGFR-3 levels in MetS and atherosclerosis.