Li Gang, Lu Wei-hua, Ai Rong, Yang Jian-hong, Chen Fang, Tang Zhong-zhi
Emergency Department, Wuhan General Hospital of Guangzhou Military Command, Wu Luo Road, Hong Shan, Wuhan, China.
Cardiovasc Diabetol. 2014 Feb 24;13:52. doi: 10.1186/1475-2840-13-52.
Hypoxia-inducible factor 1 (HIF-1), a master regulator of oxygen homeostasis, is a heterodimer consisting of HIF-1α and HIF-1β subunits, and is implicated in calcification of cartilage and vasculature. The goal of this study was to determine the relationship between serum HIF-1α with coronary artery calcification (CAC) in patients with type 2 diabetes.
The subjects were 405 (262 males, 143 females, age 51.3 ± 6.4 years) asymptomatic patients with type 2 diabetes mellitus. Serum HIF-1α and interleukin-6 (IL-6) levels were measured by ELISA. CAC scores were assessed by a 320-slice CT scanner. The subjects were divided into 4 quartiles depending on serum HIF-1α levels.
Average serum HIF-1α was 184.4 ± 66.7 pg/ml. Among patients with higher CAC scores, HIF-1α levels were also significantly increased (p <0.001). HIF-1α levels positively correlated with CRP, IL-6, UKPDS risk score, HbA1c, FBG, and CACS, but did not correlate with diabetes duration, age, and LDL. According to the multivariate analysis, HIF-1α levels significantly and independently predict the presence of CAC. ROC curve analysis showed that the serum HIF-1α level can predict the extent of CAC, but the specificity was lower than the traditional risk factors UKPDS and HbA1c.
As a marker of hypoxia, serum HIF-1α level may be an independent risk factor for the presence of CAC. These findings indicate that elevated serum HIF-1α may be involved in vascular calcification in patients with type 2 diabetes mellitus.
缺氧诱导因子1（HIF-1）是氧稳态的主要调节因子，是一种由HIF-1α和HIF-1β亚基组成的异二聚体，与软骨和血管钙化有关。本研究的目的是确定2型糖尿病患者血清HIF-1α与冠状动脉钙化（CAC）之间的关系。
研究对象为405例（男性262例，女性143例，年龄51.3±6.4岁）无症状2型糖尿病患者。采用酶联免疫吸附测定法（ELISA）检测血清HIF-1α和白细胞介素-6（IL-6）水平。通过320层CT扫描仪评估CAC评分。根据血清HIF-1α水平将研究对象分为4个四分位数。
血清HIF-1α平均水平为184.4±66.7 pg/ml。在CAC评分较高的患者中，HIF-1α水平也显著升高（p<0.001）。HIF-1α水平与CRP、IL-6、英国前瞻性糖尿病研究（UKPDS）风险评分、糖化血红蛋白（HbA1c）、空腹血糖（FBG）和CAC评分呈正相关，但与糖尿病病程、年龄和低密度脂蛋白（LDL）无关。多因素分析显示，HIF-1α水平可显著独立预测CAC的存在。ROC曲线分析表明，血清HIF-1α水平可预测CAC的程度，但其特异性低于传统危险因素UKPDS和HbA1c。
作为缺氧的标志物，血清HIF-1α水平可能是CAC存在的独立危险因素。这些发现表明，血清HIF-1α升高可能参与2型糖尿病患者的血管钙化。
