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.
- Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
- School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
- 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.