Elevated plasma miRNA-122, -140-3p, -720, -2861, and -3149 during early period of acute coronary syndrome are derived from peripheral blood mononuclear cells

PLoS One. 2017 Sep 29;12(9):e0184256. doi: 10.1371/journal.pone.0184256. eCollection 2017.

Abstract

Objective: Our previous study has found that circulating microRNA (miRNA, or miR) -122, -140-3p, -720, -2861, and -3149 are significantly elevated during early stage of acute coronary syndrome (ACS). This study was conducted to determine the origin of these elevated plasma miRNAs in ACS.

Methods: qRT-PCR was performed to detect the expression profiles of these 5 miRNAs in liver, spleen, lung, kidney, brain, skeletal muscles, and heart. To determine their origins, these miRNAs were detected in myocardium of acute myocardial infarction (AMI), and as well in platelets and peripheral blood mononuclear cells (PBMCs, including monocytes, circulating endothelial cells (CECs) and lymphocytes) of the AMI pigs and ACS patients.

Results: MiR-122 was specifically expressed in liver, and miR-140-3p, -720, -2861, and -3149 were highly expressed in heart. Compared with the sham pigs, miR-122 was highly expressed in the border zone of the ischemic myocardium in the AMI pigs without ventricular fibrillation (P < 0.01), miR-122 and -720 were decreased in platelets of the AMI pigs, and miR-122, -140-3p, -720, -2861, and -3149 were increased in PBMCs of the AMI pigs (all P < 0.05). Compared with the non-ACS patients, platelets miR-720 was decreased and PBMCs miR-122, -140-3p, -720, -2861, and -3149 were increased in the ACS patients (all P < 0.01). Furthermore, PBMCs miR-122, -720, and -3149 were increased in the AMI patients compared with the unstable angina (UA) patients (all P < 0.05). Further origin identification revealed that the expression levels of miR-122 in CECs and lymphocytes, miR-140-3p and -2861 in monocytes and CECs, miR-720 in monocytes, and miR-3149 in CECs were greatly up-regulated in the ACS patients compared with the non-ACS patients, and were higher as well in the AMI patients than that in the UA patients except for the miR-122 in CECs (all P < 0.05).

Conclusion: The elevated plasma miR-122, -140-3p, -720, -2861, and -3149 in the ACS patients were mainly originated from CECs and monocytes.

MeSH terms

  • Acute Coronary Syndrome / blood*
  • Acute Coronary Syndrome / genetics
  • Animals
  • Gene Expression Profiling
  • Humans
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • MicroRNAs / blood*
  • Real-Time Polymerase Chain Reaction
  • Swine
  • Swine, Miniature
  • Tissue Distribution

Substances

  • MicroRNAs

Grants and funding

This study was supported by National Basic Research Program (973 Program) in China (No. 2011CB503901 to Dong-Feng Gu and 2012CB518602 to Yue-Jin Yang), China Postdoctoral Science Foundation (No. 2012M510355) to Xiang-Dong Li, CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2016-I2M-1-009) to Yue-Jin Yang, and the National Science Foundation of China (No. 81270334) to Lai-Yuan Wang. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.