Journal
CIRCULATION-CARDIOVASCULAR GENETICS
Volume 3, Issue 3, Pages 300-U171Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCGENETICS.109.914556
Keywords
angiopoietins; vascular remodeling; heritability; metabolic syndrome; CVD risk factors; epidemiology; growth substances
Funding
- National Institutes of Health, National Heart, Lung, and Blood Institute [N01-HC-25195, 2 K24 HL04334, R01 HL 077477, T32 HL007572, R01 HL70100]
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Background-Experimental studies suggest that endothelial growth factors play an important role in angiogenesis and vascular remodeling. The clinical and genetic correlates of circulating angiopoietin-2 (Ang-2) and its soluble receptor/regulator Tie-2 (sTie-2) have not been determined in a community-based sample. Methods and Results-Serum Ang-2 and sTie-2 were assayed in 3778 third-generation cohort participants of the Framingham Heart Study (mean age, 40 +/- 9 years; 53% women). Clinical correlates and heritability of both biomarkers were assessed using generalized estimating equations and variance-component analyses. Ang-2 levels were higher and sTie-2 levels were lower in women than in men. Ang-2 was positively related to age, smoking, systolic blood pressure, hypertension treatment, and diabetes (P<0.05 for all) but was inversely associated with total cholesterol and diastolic blood pressure (P<0.0001 for both), and sTie-2 was positively associated with body mass index, diabetes, and triglycerides but was inversely related to age, alcohol consumption, and glomerular filtration rate (P<0.05 for all). Both Ang-2 and sTie-2 were higher in participants with metabolic syndrome (P<0.005), with stronger associations of Ang-2 with blood pressure traits and of sTie-2 with obesity-dyslipidemia components. Heritability estimates for Ang-2 and sTie-2 were 27% and 56%, respectively (P<0.0001). A region on chromosome 9 was significantly linked to circulating sTie-2 levels (logarithm of the odds score, 8.31). Conclusion-Circulating levels of Ang-2 and sTie-2 are heritable traits associated with cardiovascular disease risk factors, including the metabolic syndrome. These observations are consistent with the notion that angiogenesis and vascular remodeling are determined in part by genetic influences and associated with metabolic risk factors. (Circ Cardiovasc Genet. 2010; 3: 300-306.)
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