冠心病患者血浆微小RNA-221和微小RNA-222与侧支循环形成的相关性研究

目的观察冠心病患者血浆中微小RNA-221和微小RNA-222水平与冠状动脉侧支循环形成的关系。方法连续入选在首都医科大学附属北京安贞医院心内科接受选择性冠状动脉造影检查，证实左前降支、左回旋支或右冠状动脉中单支血管狭窄≥95％的冠心病患者120例，根据Rentrop分级将患者分成2组：侧支良好组（Rentropf〉2级）（n=64），侧支不良组（Rentrop≤1级）（n=56）。采用实时荧光定量-聚合酶链反应（qRT-PCR）检测血浆微小RNA-221和微小RNA-222的表达水平，酶联免疫吸附试验（ELISA）检测札清中c-kit和内皮源性-氧化氮合酶（eNOS）的浓度。采用Pearson相关分析和Logistic回归进行相关性分析。，结果侧支不良组血浆中微小RNA-221和微小RNA-222水平明显高于侧支良好组（0．25±0．04比0．13±0．03；0．21±0．06比0．12±0．02，P=0．001和P=0．003）。侧支不良组血清c-kit和eNOS水平低于侧支良好组[（3．8±1．3）μg／L比（6．2±2．3）μg／L；（18．7±5．5）μg/L比（24．9±8．0）μg／L，二者均P〈0．05]。侧支良好组和侧支不良组血液中微小tlNA-22l和微小RNA-222与c-kit和eNOS明显负相关[（侧支良好组微小RNA-221与c-kit：r=-0．581，P=0．012；微小RNA-221与eNOS：r=-0．534，P=0．019；侧支不良组微小RNA-221与c-kit：r=-0．653，P=0．021；微小RNA-221与eNOS：r=-0．061，P=0．028）、（侧支良好组微小RNA-222与c-kit：r=-0．495，P=0．004；微小RNA-222与eNOS：r=-0．483，P：0．022；侧支不良组侧支良好组微小RNA-222与c-kit：r=-0．638，P=0．035；微小ItNA-222与eNOS：r=-0．623，P=0．015]，而健康对照组中微小RNA-221／微小RNA-222与c-kit和eNOS没有明显相关性（微小IINA-221与c-kjt：r=-0．075，P=0．676；微小RNA-222与c-kit：r=-0．058，P=0．722；微小RNA-221与eNOS：r=-0．084，P=0．342；微小RNA-222与eNOS：r=-0．045，P=0．812）．，微小RNA-221和微小RNA-222是冠状动脉侧支循环形成的独立预测因子[比值比（OR）=2．246，P=0．012；OR=2．373，P=0．003）]。结论血浆微小RNA-221和微小RNA-222水平与冠状动脉侧支循环形成明显负相关，是冠状动脉侧支循环形成的独立预测因素。

Correlation of microRNA-221/222 plasma levels in coronary collaterals patients with coronary artery disease

Objective To study the relationship between plasma microRNA-221 and microRNA-222 （miR-221/222） levels and coronary collateral circulation （CCC） formation in patients with severely narrowed coronary arteries. Methods A total of 120 patients with coronary heart disease in Beijing Anzhen Hospital who had 95% or greater of stenosis in one epicardial coronaFy artery were enrolled consecutively. They were divided into two groups according to Rentrop grades： patients with grade 2 and 3 collateral development were regarded as good CCC group （n = 64 ） and patients with grade 0-1 collateral development were regarded as poor CCC group （ n = 56 ）. Plasma miR-221/222 was measured by real-time quantitative-polymerase chain reaction （qRT-PCR） and serum c-kit and endothelial nitric oxide synthase （eNOS） were evaluated by enzyme linked immunosorbent assay （ELISA）. The data were statistically analyzed by Pearson and Logistic correlation analysis. Results Compared with poor CCC patients, patients with good CCC had lower miR-221/222 levels [0.25 ± 0.04 vs 0.13 ± 0.03, 0.21 ±0.06 vs 0.12 ±0.02, P =0.001, P =0. 003 ] and higher c-kit and eNOS levels [ （3.8 ± 1.3 ） μg/L vs （ 6.2 ± 2.3 ） μg/L, and （ 18.7 ± 5.5 ） μg/L vs （ 24.9± 8.0 ） μg/L]. In CAD patients with good CCC and poor CCC, the miR-221/222 levels were negatively correlated to the c-kit and eNOS expression [ Good CCC group： miR-22 i and c-kit expression（ r -= - 0. 581, P = 0. 012） , miR-221 and eNOS （ r = - 0. 534, P = 0.019 ） ; Poor CCC group：miR-221 and c-kit expression（r = -0. 653, P =-0. 021 ） mitt-221 and eNOS （r = -0. 661, P = 0. 028 ）. Good CCC group ： miR-221 and c-kit （ r = - 0. 638, P = 0. 035 ） ; miR-222 and c-kit （ r = - 0. 495, P = 0. 004） ;miR-222 and eNOS（r = -0. 483, P =0. 022） ; Poor CCC group：miR-222 and eNOS（r = -0. 623, P =0. 015）. Of the healthy people, there were no significant relationship among miR-221/222 and c-kit or eNOS（ miR-221 and c-kit： r = -0.075, P =0.676; miR-222 and c-kit：r= -0.058, P =0.722; miR-221and eNOS：r= -0.084, P =0.342; miR- 222 and eNOS：r = -0. 045, P = 0. 812）. In multivariate analysis, plasma miR-221/222 was an independent predictor of collateral development （ OR = 2. 246, P = 0.012 and OR = 2. 373, P = 0. 003）. Conclusion Plasma miR-221/222 levels are closely related to the CCC formation and are independent predictors of CCC development.