Lieb Wolfgang, Zachariah Justin P, Xanthakis Vanessa, Safa Radwan, Chen Ming-Huei, Sullivan Lisa M, Larson Martin G, Smith Holly M, Yang Qiong, Mitchell Gary F, Vita Joseph A, Sawyer Douglas B, Vasan Ramachandran S
Framingham Heart Study, Framingham, MA 01702-5803, USA.
Circ Cardiovasc Genet. 2010 Jun;3(3):300-6. doi: 10.1161/CIRCGENETICS.109.914556. Epub 2010 Mar 26.
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.
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).
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.
实验研究表明，内皮生长因子在血管生成和血管重塑中起重要作用。尚未在基于社区的样本中确定循环血管生成素-2（Ang-2）及其可溶性受体/调节因子Tie-2（sTie-2）的临床和遗传相关性。
对弗雷明汉心脏研究的3778名第三代队列参与者（平均年龄40±9岁；53%为女性）进行血清Ang-2和sTie-2检测。使用广义估计方程和方差成分分析评估这两种生物标志物的临床相关性和遗传力。女性的Ang-2水平高于男性，sTie-2水平低于男性。Ang-2与年龄、吸烟、收缩压、高血压治疗和糖尿病呈正相关（均P<0.05），但与总胆固醇和舒张压呈负相关（均P<0.0001），sTie-2与体重指数、糖尿病和甘油三酯呈正相关，但与年龄、饮酒量和肾小球滤过率呈负相关（均P<0.05）。代谢综合征参与者的Ang-2和sTie-2水平均较高（P<0.005），Ang-2与血压特征的关联更强，sTie-2与肥胖-血脂异常成分的关联更强。Ang-2和sTie-2的遗传力估计分别为27%和56%（P<0.0001）。9号染色体上的一个区域与循环sTie-2水平显著相关（优势对数评分，8.31）。
Ang-2和sTie-2的循环水平是与心血管疾病危险因素（包括代谢综合征）相关的可遗传性状。这些观察结果与血管生成和血管重塑部分由遗传影响决定并与代谢危险因素相关的观点一致。
