急性冠脉综合征患者血清miR-22/133a水平与冠脉病变严重程度的相关性分析

Correlation Analysis of Serum miR-22/133a Level and Severity of Coronary Lesions in Patients with Acute Coronary Syndrome

摘要: 背景：急性冠脉综合征(acute coronary syndrome, ACS)作为心血管领域中一类极为严重且复杂的疾病，已然成为全球公共卫生体系的沉重负担。寻找新的生物标志物和治疗靶点仍是心血管领域亟待解决的关键问题。miRNA-22和miRNA-133a作为在心血管系统中高表达并发挥重要调控作用的miRNA，已有研究充分表明它们深度参与了心血管疾病的多种病理生理过程。本研究对miRNA-22/133a在ACS患者中的表达水平变化及其与冠脉病变严重程度的相关性做进一步临床研究。目的：本研究旨在分析急性冠脉综合征(Acute coronary syndrome, ACS)患者血清miRNA22与miRNA133a表达水平与冠脉病变严重程度的相关性及其对ACS患者的预后有无预测价值。方法：本研究连续收集2023年1月至2024年2月于泰州市人民医院心血管内科住院的ACS患者187例。收集受试者的一般资料、过往病史、实验室检验指标，并在冠状动脉造影术前，经受试者右侧桡动脉或股动脉采集5 ml血液样本，提取出总RNA，利用实时荧光定量PCR (Real-time fluorescent quantitative PCR, RT-qPCR)技术获取血清miRNA-22/133a的相对表达水平。结果：(1) 血清miRNA-22/133a相对表达水平在不同组间的对比：相较于对照组，ACS组血清miRNA-22/133a相对表达水平显著升高，差异均具有统计学意义(P < 0.05)。与对照组相比，UA组以及AMI组的血清miRNA-22/133a相对表达水平也显著上升，差异具有统计学意义(P < 0.05)。但UA组与AMI组相比，血清miRNA-22/133a水平差异均不具有统计学意义(P > 0.05)。(2) 血清miRNA-22/133a相对表达水平和Gensini评分的相关性分析：血清miRNA–22/133a (β = 0.274, P < 0.001/β = 0.378, P < 0.001)与Gensini评分均呈正相关｡(3) ACS的Logistic回归：血清miRNA-22 OR值1.433，95% CI：1.089~1.641，P = 0.011，表明血清miRNA-22是ACS发病的危险因素；血清miRNA-133a OR值1.877，95% CI：0.934~2.356，P = 0.013，表明血清miRNA-133a是ACS发病的危险因素｡(4) ROC曲线分析：血清miRNA-22/133a用于诊断冠状动脉狭窄程度 ≥ 50%的效能评估，其曲线下面积(Area under curve, AUC)及95%可信区间(Confidence interval, CI)分别为0.846 (0.759~0.933)､0.808 (0.720~0.895)；二者联合检测(AUC (95% CI): 0.892 (0.823~0.961))优于血清miRNA-22和miRNA-133a各自单独诊断。结论：(1) ACS患者血清中miRNA-22/133a水平均显著上升；(2) 血清miRNA-22/133a水平与冠脉病变严重程度呈正相关；(3) 血清miRNA-22/133a均为ACS发生的危险因素；(4) 血清miRNA-22/133a有望成为诊断冠状动脉狭窄生物标志物。

Abstract: Background: Acute coronary syndrome (ACS), as an extremely serious and complex disease in the cardiovascular field, has become a heavy burden on the global public health system. The search for new biomarkers and therapeutic targets remains a key issue in the cardiovascular field. miRNA-22 and miRNA-133a, which are highly expressed and play an important regulatory role in the cardiovascular system, have been fully demonstrated that they are deeply involved in various pathophysiological processes of cardiovascular diseases. In this study, the expression level of miRNA-22/133a in ACS patients and its correlation with the severity of coronary lesions were further studied. Objective: To analyze the correlation between the expression levels of serum miRNA22 and miRNA133a and the severity of coronary lesions in patients with acute coronary syndrome (ACS), and their predictive value for the prognosis of ACS patients. Methods: In this study, 187 patients with ACS who were hospitalized in the Cardiovascular Department of Taizhou People’s Hospital from January 2023 to February 2024 were continuously collected. General information, past medical history and laboratory test indicators of the subjects were collected. 5 ml blood samples were collected from the subjects’ right radial artery or femoral artery before coronary angiography, and total RNA was extracted. Real-time fluorescent quantitative PCR (RT-qPCR) was used to obtain the relative expression level of serum miRNA-22/133a. Results: (1) Comparison of the relative expression level of serum miRNA-22/133a between different groups: Compared with the control group, the relative expression level of serum miRNA-22/133a in the ACS group was significantly increased, with statistical significance (P < 0.05). Compared with the control group, the relative expression level of serum miRNA-22/133a in UA and AMI groups was also significantly increased, with statistical significance (P < 0.05). However, there was no significant difference in serum miRNA-22/133a level between the UA group and AMI group (P > 0.05). (2) Correlation analysis between the relative expression level of serum miRNA-22/133a and Gensini score: Serum miRNA-22/133a (β = 0.274, P < 0.001/β = 0.378, P < 0.001) was positively correlated with Gensini score. (3) Logistic regression of ACS: serum miRNA-22 OR value was 1.433, 95% CI:1.089~1.641, P = 0.011, indicating that serum miRNA-22 was a risk factor for the onset of ACS. The OR value of serum miRNA-133a was 1.877, 95% CI: 0.934~2.356, P = 0.013, indicating that serum miRNA-133a was a risk factor for the incidence of ACS. (4) ROC curve analysis: evaluation of the efficacy of serum miRNA-22/133a in diagnosing coronary artery stenosis ≥ 50%. The Area under the curve (AUC) and 95% Confidence interval (CI) were 0.846 (0.759~0.933) and 0.808 (0.720~0.895), respectively. Combined detection (AUC (95% CI): 0.892 (0.823~0.961)) was superior to the separate detection of serum miRNA-22 and miRNA-133a. Conclusion: (1) Serum miRNA-22/133a levels in ACS patients were significantly increased; (2) The level of serum miRNA-22/133a was positively correlated with the severity of coronary lesions; (3) Serum miRNA-22/133a were risk factors for ACS. (4) Serum miRNA-22/133a is expected to be a biomarker for the diagnosis of coronary artery stenosis.