Clinical and pathogenetic significance of angiogenesis factors (VEGF-A, HGF, IGF-1) in the development of cardiometabolic disorders in gout patients having different obesity phenotypes

Abstract

Aim. To study such circulating angiogenesis factors as vascular endothelial growth factor (VEGF-A), hepatocyte growth factor (HGF), insulin-like growth factor (IGF-1), as well as the cytokine profile (IL-1β, TNF-α, IL-6, IL-8, IL-23) and their soluble receptors (SRp55 TNF-α, SR IL-6) in the blood serum of gout patients having various obesity phenotypes.Material and methods. The study included 112 male patients with intercritical gout. The patients were divided into 2 study groups: the 1st group consisted of 39 patients with a metabolically healthy obesity (MHO) phenotype and body mass index (BMI) ≥25 kg/m2; the 2nd group included 73 people having metabolically unhealthy obesity (MUO) with impaired immune status, hypertension (HTN) and class 1 abdominal obesity. The control group consisted of 25 metabolically healthy subjects with normal body weight. Serum concentration of uric acid, CRP, insulin, leptin, insulin resistance index (HOMA-IR), cytokine status, plasma levels of VEGF-A, HGF, IGF-1 were studied. To assess the left ventricular (LV) diastolic function, tissue Doppler imaging of the mitral annulus was used.Results. In the group of patients with MUO, an increase of pro-inflammatory cytokines (IL-1β, IL-6, IL-23, TNF-α, SRp55 TNF-α) was revealed, while the level of TNF-α and IL-1β exceeds the control values in 4,7 and 6,8 times, respectively (p <0,05), and in the group of patients with MHO, 1,4 and 1,6 times, respectively (p<0,05). Correlations between VEGF-A and TNF-α (r=0,59, p<0,0001), IL-6 (r=0,68, p<0,001), CRP (r=0,59, p<0,0001), serum uric acid level (r=0,47, p<0,0001), decrease in high-density lipoprotein cholesterol (HDL-C) (r=-0,28, p<0,05) and diastolic blood pressure (r=0,51, p<0,0001) were determined. The concentration of HGF and VEGF-A correlated with BMI (p<0,001). Associations of IGF-1 and HGF with hyperuricemia, carbohydrate metabolism and diastolic remodeling were established.Conclusion. The relationship between circulating levels of VEGF-A, HGF and IGF-1 with indicators of cytokine status, carbohydrate metabolism and Doppler imaging criteria for LV diastolic dysfunction allows to consider them as additional predictors of unfavorable cardiovascular risk.

Keywords

• gout
• obesity
• growth factors
• cytokines
• diastolic dysfunction