Department of Cardiac and Vascular Diseases, John Paul II Hospital, Krakow, Poland.
Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Krakow, Poland.
J Cell Mol Med. 2018 Apr;22(4):2514-2517. doi: 10.1111/jcmm.13535. Epub 2018 Jan 29.
It is unknown whether fibrosis-associated microRNAs: miR-21, miR-26, miR-29, miR-30 and miR-133a are linked to cardiovascular (CV) outcome. The study evaluated the levels of extracellular matrix (ECM) fibrosis and the prevalence of particular microRNAs in patients with dilated cardiomyopathy (DCM) to investigate any correlation with CV events.
Seventy DCM patients (48 ± 12 years, EF 24.4 ± 7.4%) underwent right ventricular biopsy. The control group was comprised of 7 patients with CAD who underwent CABG and intraoperative biopsy. MicroRNAs were measured in blood and myocardial tissue via qPCR. The end-point was a combination of CV death and urgent HF hospitalization at the end of 12 months. There were differential levels of circulating and myocardial miR-26 and miR-29 as well as myocardial miR-133a when the DCM and CABG groups were compared. Corresponding circulating and myocardial microRNAs did not correlate with one another. There was no correlation between microRNA and ECM fibrosis. By the end of the 12-month period of the study, CV death had occurred in 6 patients, and a further 19 patients required urgent HF hospitalization. None of the circulating microRNAs was a predictor of the combined end-point; however, myocardial miR-133a was an independent predictor in unadjusted models (HR 1.53; 95% CI 1.14-2.05; P < .004) and adjusted models (HR 1.57; 95% CI 1.14-2.17; P < .005). The best cut-off value for the miR-133a level for the prediction of the combined end-point was 0.74 ΔCq, with an AUC of 0.67. The absence of a correlation between the corresponding circulating and myocardial microRNAs calls into question their cellular source. This study sheds new light on the role of microRNAs in ECM fibrosis in DCM, which warrants further exploration.
尚不清楚纤维化相关 microRNAs(miR-21、miR-26、miR-29、miR-30 和 miR-133a)是否与心血管(CV)结局相关。本研究评估了扩张型心肌病(DCM)患者细胞外基质(ECM)纤维化水平和特定 microRNAs 的流行程度,以研究其与 CV 事件的任何相关性。
70 例 DCM 患者(48±12 岁,EF 24.4±7.4%)接受右心室活检。对照组由 7 例接受 CABG 手术和术中活检的 CAD 患者组成。通过 qPCR 测量血液和心肌组织中的 microRNAs。终点为 12 个月时 CV 死亡和紧急 HF 住院的联合终点。与 CABG 组相比,DCM 组循环和心肌 miR-26 和 miR-29 以及心肌 miR-133a 的水平存在差异。相应的循环和心肌 microRNAs 彼此之间没有相关性。microRNA 与 ECM 纤维化之间没有相关性。在研究的 12 个月期间结束时,6 例患者发生 CV 死亡,另有 19 例患者需要紧急 HF 住院。没有一种循环 microRNA 是联合终点的预测因子;然而,心肌 miR-133a 在未调整模型(HR 1.53;95%CI 1.14-2.05;P<.004)和调整模型(HR 1.57;95%CI 1.14-2.17;P<.005)中是独立的预测因子。miR-133a 水平预测联合终点的最佳截断值为 0.74ΔCq,AUC 为 0.67。相应的循环和心肌 microRNAs 之间不存在相关性,这使其细胞来源受到质疑。本研究为 microRNAs 在 DCM 中 ECM 纤维化中的作用提供了新的认识,值得进一步探索。