环状RNA circDYSF在不同类型冠心病患者外周血中的表达及临床价值探讨Expression analysis and clinical significance of circular RNA circDYSF in patients with different types of coronary artery disease
赵静雯,于海奕,张永珍,高炜
摘要(Abstract):
目的 探讨环状RNAcircDYSF在不同类型冠心病患者外周血中的表达水平及其临床价值。方法 前瞻性研究入组2018年8月至2020年6月在北京大学第三医院就诊的不同类型冠心病患者,包括慢性冠状动脉综合征(CCS)、不稳定型心绞痛(UAP)和ST段抬高型心肌梗死(STEMI)各50例。以同期经临床及冠状动脉造影除外冠心病的患者43例为对照组。采用高通量测序检测circDYSF在不同类型冠心病患者外周血中的表达量。Pearson或Spearman分析评价circDYSF表达量与心肌损伤标志物及冠状动脉病变Gensini评分的相关性。对行血管内光学相干断层成像(OCT)的患者进行亚组分析,探索circDYSF在稳定斑块组及不稳定斑块组的表达差异。通过生物信息学分析circDYSF调控的靶基因并预测其可能参与的生物学过程。结果 circDYSF在冠心病患者中的表达量(36.22±18.44)TPM高于对照组(24.63±15.38)TPM(P=0.008),其中STEMI组患者最高(40.65±25.62)TPM,其次为UAP组(31.40±14.81)TPM和CCS组(28.17±14.09)TPM,三组相比较,差异有统计学意义(P=0.031)。circDYSF表达量与冠心病患者心肌肌钙蛋白T(r=0.379,P<0.001)、肌酸激酶同工酶(r=0.362,P<0.001)以及N末端B型脑钠肽前体(r=0.166,P=0.012)正相关,与左心室射血分数负相关(r=–0.336,P<0.001)。circDYSF表达量与冠状动脉病变Gensini评分呈正相关(r=0.287,P<0.001)。亚组分析显示,circDYSF在不稳定斑块组中的表达水平高于稳定斑块组[48.62(39.02,74.68)TPM比29.32(20.89,45.65)TPM,P=0.043],其识别不稳定斑块的曲线下面积为0.77(95%CI0.53~0.93,P=0.017),敏感度90.0%,特异度60.0%。circDYSF调控的下游基因显著富集于溶酶体途径和腺苷酸活化蛋白激酶信号通路等。结论 circDYSF在不同类型冠心病中存在差异,STEMI时表达量更高;circDYSF与斑块不稳定有关,可能有助于不同类型冠心病的鉴别诊断。
关键词(KeyWords): 冠心病;环状RNA;生物标志物;不稳定斑块
基金项目(Foundation): 国家重点研发计划基金项目(2017YFC0908701)
作者(Author): 赵静雯,于海奕,张永珍,高炜
参考文献(References):
- [1] Chen LL. The expanding regulatory mechanisms and cellular functions of circular RNAs[J]. Nat Rev Mol Cell Biol, 2020,21(8):475-490.
- [2] He AT, Liu J, Li F, et al. Targeting circular RNAs as a therapeutic approach:current strategies and challenges[J].Signal Transduct Target Ther, 2021,6(1):185.
- [3] Knuuti J, Wijns W, Saraste A, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes[J].Eur Heart J, 2020,41(3):407-477.
- [4] Jneid H, Anderson JL, Wright RS, et al. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/Non-ST-elevation myocardial infarction(updating the 2007 guideline and replacing the 2011 focused update):a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines[J].Circulation, 2012,126(7):875-910.
- [5] Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction(2018)[J]. Circulation,2018,138(20):e618-e651.
- [6] Tearney G J, Regar E, Akasaka T, et al. Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies:a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation[J]. J Am Coll Cardiol, 2012,59(12):1058-1072.
- [7] Higuma T, Soeda T, Abe N, et al. A combined optical coherence tomography and intravascular ultrasound study on plaque rupture,plaque erosion, and calcified nodule in patients with ST-segment elevation myocardial infarction:incidence, morphologic characteristics, and outcomes after percutaneous coronary intervention[J]. JACC Cardiovasc Interv, 2015,8(9):1166-1176.
- [8] Johnson T W,R?ber L,Mario C,et al. Clinical use of intracoronary imaging. Part 2:acute coronary syndromes, ambiguous coronary angiography findings, and guiding interventional decision-making:an expert consensus document of the European Association of Percutaneous Cardiovascular Interventions[J]. Eur Heart J,2019,40(31):2566-2584.
- [9] Johnson T W, R?ber L, di Mario C, et al. Clinical use of intracoronary imaging. Part 2:acute coronary syndromes,ambiguous coronary angiography findings, and guiding interventional decision-making:an expert consensus document of the European Association of Percutaneous Cardiovascular Interventions[J]. Eur Heart J, 2019,40(31):2566-2584.
- [10]马丽媛,王增武,樊静,等.《中国心血管健康与疾病报告2021》概要[J].中国介入心脏病学杂志,2022,30(7):481-496.
- [11] Sumi MP, Mahajan B, Sattar R, et al. Elucidation of epigenetic landscape in coronary artery disease:a review on basic concept to personalized medicine[J]. Epigenet Insights, 2021,14:2000630679.
- [12] Zhang S, Wang W, Wu X, et al. Regulatory roles of circular rnas in coronary artery disease[J]. Mol Ther Nucleic Acids, 2020,21:172-179.
- [13]杨仕俊,周子华,陈芬.冠心病患者血液外泌体mRNA、lnc RNA及circ RNA差异表达谱及竞争性内源RNA网络的构建[J].临床心血管病杂志,2021,37(7):620-625.
- [14] Yin L, Tang Y, Jiang M. Research on the circular RNA bioinformatics in patients with acute myocardial infarction[J]. J Clin Lab Anal, 2021,35(2):e23621.
- [15] Wang L, Shen C, Wang Y, et al. Identification of circular RNA Hsa_circ_0001879 and Hsa_circ_0004104 as novel biomarkers for coronary artery disease[J]. Atherosclerosis, 2019,286:88-96.
- [16] Wen ZJ, Xin H, Wang YC, et al. Emerging roles of circRNAs in the pathological process of myocardial infarction[J]. Mol Ther Nucleic Acids, 2021,26:828-848.
- [17]梁峰,胡大一,方全,等.基于欧洲指南关于慢性冠脉综合征诊治最新进展[J].中国循证心血管医学杂志,2022,14(6):761-768.
- [18] Vergallo R, Crea F. Atherosclerotic plaque healing[J]. N Engl J Med, 2020,383(9):846-857.
- [19] Wang KY, Zheng YY, Wu TT, et al. Predictive value of gensini score in the long-term outcomes of patients with coronary artery disease who underwent PCI[J]. Front Cardiovasc Med,2021,8:778615.
- [20] Adriaenssens T, Allard-Ratick MP, Thondapu V, et al. Optical coherence tomography of coronary plaque progression and destabilization:JACC focus seminar part 3/3[J]. J Am Coll Cardiol, 2021,78(12):1275-1287.
- [21] Maehara A, Matsumura M, Ali Z A, et al. IVUS-guided versus OCT-guided coronary stent implantation:a critical appraisal[J].JACC Cardiovasc Imaging, 2017,10(12):1487-1503.
- [22] Amar Z, Talpur A S, Zafar S, et al. Comparison of iron profile in patients with and without coronary heart disease[J]. Cureus,2021,13(6):e15613.
- [23]奈文青,刘灏,王媛媛,等.差异基因表达谱分析颈动脉不稳定斑块相关基因及可能的信号通路[J].南方医科大学学报,2015,35(5):738-742.
- [24] Liang WJ, Zhou SN, Shan MR, et al. AMPKα inactivation destabilizes atherosclerotic plaque in streptozotocin-induced diabetic mice through AP-2α/mi RNA-124 axis[J]. J Mol Med(Berl),2018,96(5):403-412.
- [25] Chen Z, Zhuo R, Zhao Y, et al. Oleoylethanolamide stabilizes atherosclerotic plaque through regulating macrophage polarization via AMPK-PPARα pathway[J]. Biochem Biophys Res Commun, 2020,524(2):308-316.
- [26] Ding Y, Zhang M, Zhang W, et al. AMP-Activated protein kinase alpha 2 deletion induces VSMC phenotypic switching and reduces features of atherosclerotic plaque stability[J]. Circ Res,2016,119(6):718-730.
- [27] Wei Q, Ren H, Zhang J, et al. An inhibitor of Grp94 inhibits Ox LDL-induced autophagy and apoptosis in VECs and stabilized atherosclerotic plaques[J]. Front Cardiovasc Med, 2021,8:757591.
- [28] Wang S, Song P, Zou MH. AMP-activated protein kinase, stress responses and cardiovascular diseases[J]. Clin Sci(Lond),2012,122(12):555-573.