High retinoic acid receptor-related orphan receptor A gene expression in peripheral blood leukocytes may be related to acute myocardial infarction.
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ABSTRACT: Objective
This study aimed to investigate whether differential expression of the retinoic acid receptor-related orphan receptor A (RORA) gene is related to occurrence of acute myocardial infarction (AMI).Methods
This was a retrospective study. White blood cells of 93 patients with acute myocardial infarction and 74 patients with stable coronary artery disease were collected. Reverse transcription quantitative polymerase chain reaction and western blotting were used to measure RORA mRNA and protein expression, respectively.Results
RORA mRNA expression levels in peripheral blood leukocytes in patients with AMI were 1.57 times higher than those in patients with stable coronary artery disease. Protein RORA levels in peripheral blood of patients with AMI were increased. Binary logistic regression analysis showed that high expression of RORA was an independent risk factor for AMI, and it increased the risk of AMI by 2.990 times.Conclusion
RORA expression levels in patients with AMI is significantly higher than that in patients with stable coronary artery disease. High expression of RORA is related to AMI and it may be an independent risk factor for AMI.
SUBMITTER: Meng H
PROVIDER: S-EPMC8191083 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAcute myocardial infarction (AMI) can occur in patients with atherosclerotic disease, with or without plaque rupture. Previous studies have indicated a set of immune responses to plaque rupture. However, the specific circulating immune cell subsets that mediate inflammatory plaque rupture remain elusive.MethodsTen AMI patients were enrolled in our study (five with and five without plaque rupture; plaque characteristics were identified by optical coherence tomography). By single-cell RNA sequencing, we analyzed the transcriptomic profile of peripheral blood mononuclear cells.ResultsWe identified 27 cell clusters among 82,550 cells, including monocytes, T cells, NK cells, B cells, megakaryocytes, and CD34+ cells. Classical and non-classical monocytes constitute the major inflammatory cell types, and pro-inflammatory genes such as CCL5, TLR7, and CX3CR1 were significantly upregulated in patients with plaque rupture, while the neutrophil activation and degranulation genes FPR2, MMP9, and CLEC4D were significantly expressed in the intermediate monocytes derived from patients without plaque rupture. We also found that CD4+ effector T cells may contribute to plaque rupture by producing a range of cytokines and inflammatory-related chemokines, while CD8+ effector T cells express more effector molecules in patients without plaque rupture, such as GZMB, GNLY, and PRF1, which may contribute to the progress of plaque erosion. Additionally, NK and B cells played a significant role in activating inflammatory cells and promoting chemokine production in the plaque rupture. Cell-cell communication elaborated characteristics in signaling pathways dominated by inflammatory activation of classical monocytes in patients with plaque rupture.ConclusionsOur studies demonstrate that the circulating immune cells of patients with plaque rupture exhibit highly pro-inflammatory characteristics, while plaque erosion is mainly associated with intermediate monocyte amplification, neutrophil activation, and degranulation. These findings may provide novel targets for the precise treatment of patients with AMI.
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2024-06-12 | GSE269269 | GEO
Project description:BACKGROUND:Acute myocardial infarction (AMI) is characterized by an inflammatory process in which T cell plays a key role. However, the profile of immune microenvironment in AMI is still uncertain. High-throughput sequencing of T cell receptor (TCR) provides deep insight into monitoring the immune microenvironment. METHODS:30 patients with AMI were enrolled and 30 healthy individuals were recruited as controls. Flow cytometer were used to analyze the distribution of αβ T cells and their CD69 expression from peripheral leukomonocytes. TCRβ repertoire library was amplified by two-round multiplex PCR and detected by next-generation sequencing (NGS). RESULTS:The percentage of αβ T cells in AMI patients were significantly restricted than those in healthy controls, while the highly activated αβ T cells along with distinguishing usage of variable (V), diversity (D) and joining (J) gene segments were also found in AMI patients. In addition, AMI induced a significantly restricted CDR3 amino acid (AA) diversity and remarkably reconstituted TCR immune repertoires. Finally, we identified several AMI-associated tendency of CDR3 AAs expression after AMI. CONCLUSIONS:Our work suggests that the aberrant αβ T cells distribution and activation may associated with the pathogenesis of AMI and demonstrates a reconstitution of TCRβ immune repertoire after AMI.
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Project description:BackgroundDespite a substantial progress in diagnosis and therapy, acute myocardial infarction (MI) is a major cause of mortality in the general population. A novel insight into the pathophysiology of myocardial infarction obtained by studying gene expression should help to discover novel biomarkers of MI and to suggest novel strategies of therapy. The aim of our study was to establish gene expression patterns in leukocytes from acute myocardial infarction patients.Methods and resultsTwenty-eight patients with ST-segment elevation myocardial infarction (STEMI) were included. The blood was collected on the 1(st) day of myocardial infarction, after 4-6 days, and after 6 months. Control group comprised 14 patients with stable coronary artery disease, without history of myocardial infarction. Gene expression analysis was performed with Affymetrix Human Gene 1.0 ST microarrays and GCS3000 TG system. Lists of genes showing altered expression levels (fold change >1.5, p<0.05) were submitted to Ingenuity Pathway Analysis. Gene lists from each group were examined for canonical pathways and molecular and cellular functions. Comparing acute phase of MI with the same patients after 6 months (stable phase) and with control group we found 24 genes with changed expression. In canonical analysis three pathways were highlighted: signaling of PPAR (peroxisome proliferator-activated receptor), IL-10 and IL-6 (interleukin 10 and 6).ConclusionsIn the acute phase of STEMI, dozens of genes from several pathways linked with lipid/glucose metabolism, platelet function and atherosclerotic plaque stability show altered expression. Up-regulation of SOCS3 and FAM20 genes in the first days of myocardial infarction is observed in the vast majority of patients.
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Project description: Not available
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