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PLoS One. 2019 May 7;14(5):e0216610. doi: 10.1371/journal.pone.0216610. eCollection 2019.

High serum CRP influences myocardial miRNA profiles in ischemia-reperfusion injury of rat heart.

Author information

1
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
2
Asan Laboratory of Perinatal Science, Asan Medical Center, Seoul, Republic of Korea.
3
Department of Physiology, Asan-Minnesota Institute for Innovating Transplantation, Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
4
Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
5
Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea.

Abstract

OBJECTIVE:

Prognosis of myocardial infarction tends to be worse when serum C-reactive protein (CRP) level is high. miRNAs are also known to be involved in different pathogeneses of heart diseases such as myocardial infarction. However, how CRP is involved in myocardial infarction has not been fully elucidated. We hypothesized that serum CRP changes the miRNA profile during ischemia-reperfusion injury (IRI) of the myocardium. To confirm this hypothesis, we performed global miRNA expression profiling of myocardium using IRI and CRP infusion rat model.

METHODS:

After ligation of the coronary artery of rat hearts, human serum CRP was intravenously injected, and reperfusion was performed (I/R+CRP group, n = 6). Control group consisted of the sham group (n = 3), IV CRP infusion group (CRP only, n = 3), and the I/R-only group (I/R only, n = 5). We evaluated 423 miRNA expression in non-ischemic areas and areas at risk (AAR) of each group using NanoString nCounter miRNA expression assay.

RESULTS:

MiR-124 was downregulated in non-ischemic myocardium in CRP-only group. In AAR, 7 miRNAs were commonly upregulated in both I/R-only and I/R+CRP groups. And additional 6 miRNAs were upregulated in the I/R+CRP group (miR-33, miR-409-3p, miR-384-3p, miR-3562, miR-101a, and miR-340-5p). Similarly, in the non-ischemic areas, 6 miRNAs were commonly upregulated in both I/R-only and I/R+CRP groups, and additional 5 miRNAs changed in the I/R+CRP group (upregulation of miR-3559-5p, miR-499, and miR-21 and downregulation of miR-500 and miR-532-3p).

CONCLUSION:

We showed that when serum CRP level is high, IRI results in multiple miRNA profile changes not only in ischemic areas but also in non-ischemic myocardium. Our results may provide a strong basis for studying the role of CRP and miRNAs in ischemic heart disease.

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