Effects of trimetazidine on periprocedural microRNA-21 expression by CD4+ T lymphocytes in patients with unstable angina pectoris.

Qiang Su,Jinmin Zhao,Lang Li,Yuhan Sun,Huafeng Yang

doi:10.18632/oncotarget.20975

Abstract

ObjectivePost-percutaneous coronary intervention (PCI) myocardial injury is related to the CD4+ T lymphocyte-mediated inflammatory response. microRNA-21 expression is associated with CD4+ T lymphocyte activation. The pre-PCI use of trimetazidine prevents periprocedural myocardial injury and reduces inflammatory cytokine levels. This study aimed to assess the effects of trimetazidine on periprocedural microRNA-21 expression by CD4+ T lymphocytes in patients with unstable angina pectoris.MethodsA total of 252 patients with unstable angina pectoris were randomized to the trimetazidine (60 mg/d, administered 3 days before PCI, n=128) and control (no trimetazidine, n=124) groups. Serum CK-MB, cTnI, and hs-CRP levels were tested pre-PCI and 16-24 h post-PCI. Peripheral blood CD4+ T lymphocytes were isolated by magnetic activated cell sorting. Quantitative polymerase chain reaction was used to assess microRNA-21 and PDCD4 mRNA expression levels in CD4+ T lymphocytes, and western blot was used to evaluate PDCD4 protein expression. Enzyme-linked immunosorbent assay was used to assess serum TNF-α and IL-10 levels.ResultsCompared with the control group, the trimetazidine group had a lower frequency of patients with post-PCI serum CK-MB and cTnI levels higher than normal values; the trimetazidine group had also significantly lower serum hs-CRP and TNF-α levels, and higher IL-10 levels post-PCI. Finally, the trimetazidine group had significantly lower PDCD4 expression and higher microRNA-21 levels in CD4+ T lymphocytes post-PCI.ConclusionsTrimetazidine reduces the incidence of periprocedural myocardial injury, possibly by increasing microRNA-21 levels in CD4+ T lymphocytes and inhibiting PDCD4-mediated inflammatory response.

Highlights

Periprocedural myocardial injury (PMI) is a frequent complication of percutaneous coronary intervention (PCI), especially among high-risk patients with acute coronary syndrome (ACS)
Compared with the control group, the trimetazidine group had a lower frequency of patients with post-PCI serum creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) levels higher than normal values; the trimetazidine group had significantly lower serum high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor α (TNF-α) levels, and higher IL-10 levels post-PCI
Trimetazidine reduces the incidence of periprocedural myocardial injury, possibly by increasing microRNA-21 levels in CD4+ T lymphocytes and inhibiting programmed cell death 4 (PDCD4)-mediated inflammatory response

Summary

Introduction

Periprocedural myocardial injury (PMI) is a frequent complication of percutaneous coronary intervention (PCI), especially among high-risk patients with acute coronary syndrome (ACS). Previous studies demonstrated that post-PCI activation of local CD4+ T lymphocytes and the subsequent myocardial inflammatory response probably play a role in PMI [1]. MicroRNAs (miRNAs) are endogenous noncoding small RNA molecules of 18-25 nucleotides. They are important post-transcriptional regulatory www.impactjournals.com/oncotarget genes widely found in the non-coding regions of the genome, regulating cell proliferation, cell differentiation, inflammation, and apoptosis [2, 3]. Lu et al [4] reported that miRNA-21 downregulation in CD4+ T lymphocytes enhanced Th1 cell-mediated inflammatory response and reduced Th2 cell-secreted anti-inflammatory cytokines, indicating that miRNA-21 upregulation may inhibit the inflammatory response mediated by over-activated Th1 cells. We hypothesized that postPCI myocardial injury may be alleviated by miRNA-21 upregulation in CD4+ T lymphocytes, improving patient prognosis

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