Circulating angiopoietin-2 and its soluble receptor Tie-2 concentrations are related to inflammatory markers in the general population.

BACKGROUND: The Angiopoietin/Tie (Tyrosine kinase with Ig and EGF homology domains) signaling axis has crucial influences on angiogenesis and the vasculature's reorganization. Moreover, angiopoietin-2 (Ang2) is discussed as a biomarker for diseases' severity and development. Previous studies reported increased Ang2 levels in patients with inflammatory diseases and associations of Ang2 with inflammation markers in relatively small samples. We aimed to assess the relation of Ang2 and Tie2 with inflammation markers in the general population. METHODS AND RESULTS: Data of 6624 participants of the population-based Study of Health in Pomerania (SHIP-1) and the independent SHIP-Trend were used. Ang2, Tie2 and inflammatory biomarkers, including fibrinogen, high-sensitive C-reactive protein (hsCRP) and white blood cell count (WBC), were measured. Adjusted analysis of variance (ANOVA) and linear/logistic regression models were performed in the entire sample and in individuals free of hypertension and diabetes. ANOVA [adjusted means of the 1st vs. 4th Ang2 quartile: fibrinogen 3.0 vs. 3.2 g/l; hsCRP 1.2 vs. 1.6 mg/l; WBC 5.9 vs. 6.6 Gpt/l] and regression models adjusted for potential confounders revealed positive relations of Ang2 with all considered inflammation markers. These associations persisted after the exclusion of individuals with hypertension and diabetes. In contrast, Tie2 showed no clear association pattern with the investigated inflammatory markers even if a trend toward a positive relation with fibrinogen became apparent. CONCLUSION: Ang2 was positively associated with fibrinogen, hsCRP and WBC in a large population-based setting. These findings partly agree with previous results, largely obtained in clinical samples. Ang2 has diverse postulated effects on inflammation processes, like increase of vascular leakage or influences on the adhesion of leukocytes to the vessel wall. The proinflammatory character of these effects is similar to these of fibrinogen which conforms to our findings of relations between the markers. However, further research is needed to elucidate possible functional mechanisms.