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Peripheral blood mononuclear cell hyperresponsiveness in patients with premature myocardial infarction without traditional risk factors

ABSTRACT: Peripheral blood mononuclear cell hyperresponsiveness in patients with premature myocardial infarction without traditional risk factors

PROVIDER: PRJNA952632 | ENA |

REPOSITORIES: ENA

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Peripheral blood mononuclear cell hyperresponsiveness in patients with premature myocardial infarction without traditional risk factors

Project description:An increasing number of patients develop a myocardial infarction (MI) in the absence of standard modifiable risk factors (SMuRFs). Atherosclerosis is characterized by a chronic arterial wall inflammation in which monocyte-derived macrophages play a pivotal role. Trained immunity – a long lasting hyperreactive state of innate immune cells – might contribute to the development of atherosclerosis. This study investigated whether trained immunity is observed in this specific patient group. 20 SMuRFless MI patients who suffered an atherothrombotic myocardial infarction > 1 year and < 4 years before inclusion were recruited. All patients were younger than 50 years of age during the index event. Patients were matched to 18 healthy controls without coronary atherosclerosis as determined by a coronary CT-scan. Blood samples were obtained two weeks after interrupting statins in patients and starting aspirin therapy in controls to match relevant medication use. Circulating inflammatory parameters and monocytes were analyzed, with an in-depth focus on peripheral blood mononuclear cell (PBMC) function, and monocyte phenotype, RNA expression and epigenetic histone markers. PBMCs from SMuRFless patients showed higher cytokine production upon ex vivo stimulation. Although baseline RNA expression and monocyte activations markers were largely unchanged, enrichment of the transcriptionally permissive histone marker H3K4me3 on the promoter region of cytokine genes was observedIL-10 genes was observed. This existed without differences in systemic inflammation. Circulating monocytes in young SMuRFless MI patients have a hyperresponsive functional and epigenetic phenotype, indicative of trained immunity. In the absence of traditional risk factors, this could be a promising target for future therapy in these patients.

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Altered gene expression pattern in peripheral blood mononuclear cells in patients with acute myocardial infarction

Project description:Despite 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. ST-segment elevation myocardial infarction alters expression of several groups of genes. On admission, several genes and pathways that could be directly or indirectly linked with lipid/glucose metabolism, platelet function and atherosclerotic plaque stability were affected (signaling of PPAR, IL-10, IL-6). Analysis at discharge highlighted specific immune response (upregulation of immunoglobulins). Highly significant and substantial upregulation of SOCS3 and FAM20 genes expression in the first 4-6 days of myocardial infarction in all patients is the most robust observation of our work Twenty-eight patients with ST-segment elevation myocardial infarction (STEMI) were included. The blood was collected on the 1st day of myocardial infarction, after 4-6 days, and after 6 months. Control group comprised 14 patients with stable coronary artery disease (CAD), without history of myocardial infarction. Gene expression analysis was performed with Affymetrix GeneChipM-BM-. Human Gene 1.0 ST microarrays and GCS3000 TG system.

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myocardial infarction in Reg3beta knock-out mice

Project description:Affymetrix microarray analysis of molecular changes after myocardial infarction. Samples of heart tissue were analyzed after myocardial infarction from WT and reg3beta knock-out mice. Samples from scar tissue and samples adjacent to the scar were analyzed. In the experiment we primarily compared infarction zone of wild-type to infarction zone of knock-out animals, and remote zone of wild-type to remote zone of knock-outs.

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