From the Department of Cardiovascular Diseases, Mayo Clinic and College of Medicine, Rochester, MN (R.A., A.A., R.G., L.O.L., A.L.).
Bruce and Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel (A.P.L., N.S.L., H.G., I.S.).
Arterioscler Thromb Vasc Biol. 2019 Apr;39(4):774-786. doi: 10.1161/ATVBAHA.118.312232.
Objective- Coronary endothelial dysfunction (ED) is an early stage of atherosclerosis and is associated with impaired high-density lipoprotein (HDL) function. A functional polymorphism at the haptoglobin (Hp) gene locus (rs72294371) has been associated with marked differences in HDL structure and function. We sought to determine whether Hp phenotype was associated with coronary ED and whether the amount of hemoglobin (Hb) tethered to HDL via Hp was Hp-type dependent and associated with ED. Approach and Results- Microvascular and epicardial coronary endothelial function was assessed in 338 individuals with nonobstructive coronary artery disease. Microvascular ED was defined as <50% change in coronary blood flow and epicardial ED as ≥20% decrease in coronary artery diameter after intracoronary acetylcholine infusion. The amount of Hb bound to HDL was measured by ELISA after HDL purification from plasma samples using immune-affinity chromatography. One hundred and seventy of the individuals in this study (50.3%) were diagnosed with microvascular ED, 143 (42.3%) with epicardial ED, and 67 (19.7%) had diabetes mellitus (DM). Hp phenotype was significantly associated with microvascular ( P=0.01) and epicardial ED ( P=0.04) among DM individuals. There was a significant and inverse correlation between the amount of HDL-bound Hb and change in coronary blood flow (r=-0.40; P<0.0001) and in coronary artery diameter (r=-0.44; P<0.0001) in response to acetylcholine infusion. Hb content of HDL was significantly increased in individuals with Hp 2-2 and DM. In a logistic regression model, Hp 2-2 phenotype was associated with microvascular ED (odds ratio, 1.9; P=0.03) and the amount of HDL-bound Hb was an independent predictor of both microvascular (odds ratio, 4.6 for each 1-SD increase; P<0.0001) and epicardial (odds ratio, 2.2; P<0.0001) ED. Conclusions- Hp phenotype is significantly associated with coronary ED in DM individuals. This association is likely related to increased Hb tethering to HDL via Hp 2-2 in DM.
冠状动脉内皮功能障碍（ED）是动脉粥样硬化的早期阶段，与高密度脂蛋白（HDL）功能受损有关。在触珠蛋白（Hp）基因座的一个功能多态性（rs72294371）与 HDL 的结构和功能有显著差异有关。我们试图确定 Hp 表型是否与冠状动脉 ED 相关，以及通过 Hp 与 HDL 结合的血红蛋白（Hb）量是否依赖于 Hp 型，并与 ED 相关。
对 338 名非阻塞性冠状动脉疾病患者进行微血管和心外膜冠状动脉内皮功能评估。微血管 ED 定义为冠状动脉血流变化<50%，而心外膜 ED 定义为冠状动脉内乙酰胆碱输注后冠状动脉直径减少≥20%。通过使用免疫亲和色谱法从血浆样本中纯化 HDL 后，通过 ELISA 测量与 HDL 结合的 Hb 量。在这项研究中的 170 名个体（50.3%）被诊断为微血管 ED，143 名（42.3%）有心外膜 ED，67 名（19.7%）患有糖尿病（DM）。在 DM 个体中，Hp 表型与微血管（P=0.01）和心外膜 ED（P=0.04）显著相关。与乙酰胆碱输注后冠状动脉血流变化（r=-0.40；P<0.0001）和冠状动脉直径变化（r=-0.44；P<0.0001）呈显著负相关。与 HDL 结合的 Hb 量在 Hp 2-2 和 DM 个体中显著增加。在逻辑回归模型中，Hp 2-2 表型与微血管 ED 相关（优势比，1.9；P=0.03），与 HDL 结合的 Hb 量是微血管（优势比，每增加 1-SD 增加 4.6；P<0.0001）和心外膜（优势比，2.2；P<0.0001）ED 的独立预测因子。
在 DM 个体中，Hp 表型与冠状动脉 ED 显著相关。这种关联可能与 DM 中通过 Hp 2-2 与 HDL 结合的 Hb 量增加有关。
