Platelets induce endothelial cell mitochondrial dysfunction in myocardial infarction
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE278026 | GEO | 2025/08/29
REPOSITORIES: GEO
Similar Datasets
Project description:Platelets are central to the pathophysiology of myocardial infarction (MI). How the platelet proteome is altered during MI is unknown. We sought to describe changes in the platelet proteome at the time of MI and identify potential mechanisms. Platelets from patients experiencing ST-elevation myocardial infarction (STEMI) before and 3 days after treatment (n= 30), and a matched cohort of patients with severe stable coronary artery disease (CAD) prior to and 3 days after coronary artery bypass grafting (CABG, n=25) underwent quantitative proteomic analysis. Elevations of the alarmins S100A8 and S100A9 were detected at the time of STEMI compared with stable CAD (S100A8, FC = 2.00, FDR = 0.05; S100A9, FC = 2.28, FDR = 0.005). During STEMI, S100A8 mRNA and protein levels were correlated in platelets (R = 0.46, p = 0.012). To determine if protein synthesis occurs, activated platelets were incubated with 13C-labelled amino acids for 24 hours and analyzed by mass spectrometry. No incorporation was detected, consistent with the notion that protein synthesis in platelets is not a major contributor to the platelet proteome. Platelet abundance of S100A8 and A9 was strongly correlated with neutrophil abundance at the time of STEMI. When isolated platelets and neutrophils were co-incubated under quiescent and TRAP-6 activated conditions, release of S100A8 from neutrophils resulted in uptake of S100A8 by platelets. Leukocyte-to-platelet protein transfer, rather than protein synthesis, may occur in a thromboinflammatory environment such as STEMI, representing a potential new contributor in the innate immune pathogenesis of STEMI.
2023-11-15 | PXD024159 | Pride
Project description:Platelets are central to the pathophysiology of myocardial infarction (MI). How the platelet proteome is altered during MI is unknown. We sought to describe changes in the platelet proteome at the time of MI and identify potential mechanisms. Platelets from patients experiencing ST-elevation myocardial infarction (STEMI) before and 3 days after treatment (n= 30), and a matched cohort of patients with severe stable coronary artery disease(CAD) prior to and 3 days after coronary artery bypass grafting (CABG, n=25) underwent quantitative proteomic analysis. Elevations of the alarmins S100A8 and S100A9 were detected at the time of STEMI compared with stable CAD (S100A8, FC = 2.00, FDR = 0.05; S100A9, FC = 2.28, FDR = 0.005). During STEMI, S100A8 mRNA and protein levels were correlated in platelets (R = 0.46, p = 0.012). To determine if protein synthesis occurs, activated platelets were incubated with 13C-labelled amino acids for 24 hours and analyzed by mass spectrometry. No incorporation was detected, consistent with the notion that protein synthesis in platelets is not a major contributor to the platelet proteome. Platelet abundance of S100A8 and A9 was strongly correlated with neutrophil abundance at the time of STEMI. When isolated platelets and neutrophils were co-incubated under quiescent and TRAP-6 activated conditions, release of S100A8 from neutrophils resulted in uptake of S100A8 by platelets. Leukocyte-to-platelet protein transfer, rather than protein synthesis, may occur in a thromboinflammatory environment such as STEMI, representing a potential new contributor in the innate immune pathogenesis of STEMI.
2023-11-15 | PXD024186 | Pride
Project description:Despite the abundance of data demonstrating the critical role of platelets in myocardial infarction (MI), few studies have characterized the MI-platelet transcriptome in the acute or chronic setting. The association between MI subtype and platelet transcriptomic signature have not been explored. We report that transcripts associated with actin cytoskeleton and Rho family GTPase signaling, mitochondrial dysfunction, and inflammatory signaling are enriched in platelets from MI patients in the acute setting (n=40 MI, n=38 controls), and do not significantly change over time. We identified 79 platelet genes chronically altered post-MI that are also associated with future cardiovascular events in independent cardiovascular disease validationcohort (n=135). Compared to patients with MI with non-obstructive coronary arteries (MINOCA), platelets from patients with MI due to obstructive coronary artery disease (MI-CAD) were enriched in neutrophil activation and proinflammatory signaling pathways driven by increased TNFα signaling. Hierarchical clustering identified three MI transcriptomic subgroups with disinctive pathways and MI correlates, including a group with MI-CAD, and a group that was predominantly MINOCA. Our data demonstrate that platelets from MI patients are phenotypically different from MI-naïve patients, in the acute and chronic setting, and reveal a transcriptomic signature with distinct clinical features.
2025-04-30 | GSE272178 | GEO
Project description:Background: Myocardial infarction (MI) is the single most critical event in coronary disease. Platelets partecipate in processes that precipitate acute MI, lack nuclear DNA but retain megakaryocyte mRNAs, thus their transcriptome could provide information preceding the coronary event. Our aim was to obtain a gene expression atlas of platelets from patients with their very first acute MI (FAMI) in order to identify potential markers of precipitating factors. Methods and results: Platelets from seventeen FAMI patients and matched controls were collected and RNA and protein were purified. Expression profiles were obtained with genome-wide microarrays. Platelet-specific proteomic analysis was also performed with fluorescent DIGE separation in the same samples. Strong transcriptional down-regulation was observed in patient platelets, whereas more balanced numbers of up and down-represented proteins were found by proteomic analysis. Conclusions: Platelet transcriptome revealed quantitative differences between FAMI patients and controls. The functional analysis deregulated mRNAs and the integration with proteomic data in platelets may suggest pre-activation of platelets and/or megakaryocytes in FAMI patients before the acute event.
2017-12-31 | GSE24548 | GEO
Project description:Background: Myocardial infarction (MI) is the single most critical event in coronary disease. Platelets partecipate in processes that precipitate acute MI, lack nuclear DNA but retain megakaryocyte mRNAs, thus their transcriptome could provide information preceding the coronary event. Our aim was to obtain a gene expression atlas of platelets from patients with their very first acute MI (FAMI) in order to identify potential markers of precipitating factors. Methods and results: Platelets from seventeen FAMI patients and matched controls were collected and RNA and protein were purified. Expression profiles were obtained with genome-wide microarrays. Platelet-specific proteomic analysis was also performed with fluorescent DIGE separation in the same samples. Strong transcriptional down-regulation was observed in patient platelets, whereas more balanced numbers of up and down-represented proteins were found by proteomic analysis. Conclusions: Platelet transcriptome revealed quantitative differences between FAMI patients and controls. The functional analysis deregulated mRNAs and the integration with proteomic data in platelets may suggest pre-activation of platelets and/or megakaryocytes in FAMI patients before the acute event.
2017-12-31 | GSE24519 | GEO
Project description:Myocardial infarction (MI), the most severe manifestation of coronary artery disease, is a multifactorial pathophysiologic process. Here, we constructed a MI mouse model through ligation of the proximal left anterior descending coronary artery. Then we detected and analysed multi-omics (transcriptome and proteome) at different time points (Control, 10 mininte, 1 hour, 6 hour, 24 hour and 72 hour) after MI. Immune-related pathway, pyroptosis pathway, and autophagy pathway r were significantly increased after MI.
2021-09-14 | GSE153494 | GEO
Project description:Acute myocardial infarction (AMI) is primarily due to coronary atherosclerotic plaque rupture and subsequent thrombus formation. Platelets play a key role in the genesis and progression of both atherosclerosis and thrombosis. Since platelets are anuclear cells that inherit their mRNA from megakaryocyte precursors and maintain it unchanged during their life span, gene expression (GE) profiling at the time of an AMI provides information concerning the platelet GE preceding the coronary event. In ST-segment elevation myocardial infarction (STEMI), a gene-by-gene analysis of the platelet GE identified five differentially expressed genes (DEGs): FKBP5, S100P, SAMSN1, CLEC4E and S100A12. The logistic regression model used to combine the GE in a STEMI vs healthy donors score showed an AUC of 0.95. The same five DEGs were externally validated using platelet GE data from patients with coronary atherosclerosis but without thrombosis. Early signals of an imminent AMI are likely to be found by platelet GE profiling before the infarction occurs.
2019-12-31 | GSE109048 | GEO
Project description:Thyroid hormone improves left ventricular remodeling and cardiac performance after myocardial infarction (MI), but the molecular basis is unknown. This study was designed to detect gene expression changes in left ventricular non-infarcted areas at 4 weeks following myocardial infarction with and without thyroid hormone treatment. The results suggest that altered expression of genes for molecular function and biological process may be involved in the beneficial effects of thyroid hormone treatment following myocardial infarction in rats. MI was produced by ligation of the left anterior descending coronary artery in female SD rats. Rats were divided into the following groups: (1) Sham MI, (2) MI, and (3) MI+T4 treatment (T4 pellet 3.3mg, 60 days release, implanted subcutaneously immediately following MI). Four weeks after surgery, total RNA was isolated from left ventricular non-infarcted areas for microarray analysis using the Illumina RatRef-12 Expression BeadChip Platform.
2012-04-30 | E-GEOD-35088 | biostudies-arrayexpress
Project description:A better understanding of the pathways that regulate regeneration of the coronary vasculature is of fundamental importance for the advancement of strategies to treat patients with heart disease. By analyzing single cell transcriptome of resident cardiac endothelial cells (ECs) in adult mouse hearts under both healthy and myocardial infarction (MI) settings, we provide molecular definitions of murine cardiac endothelial heterogeneity and characterizations of pro-angiogenic resident ECs.
2019-06-18 | GSE132880 | GEO
Project description:Monocytes play a central role in the inflammatory response that follows acute myocardial infarction (MI). In order to study phenotypic adaptation of this cell type, we investigated patterns of monocyte gene expression in circulating monocytes at various stages of MI. Circulating monocytes were isolated from venous blood of MI patients at three time points: t1: within 6 hours after onset of chest pain (acute phase), t2: 3 days after MI (subacute phase), t3: 90 days after MI (chronic phase). For comparison, we studied a control group (n=21, data to be submitted later) with stable coronary artery disease. Using this transcriptomic analysis, we aimed to provide a more comprehensive reference of monocyte biology following acute MI and to aid in the identification of novel pathways and genes influencing the course of MI. Monocytes play a central role in the inflammatory response that follows acute myocardial infarction (MI). In order to study phenotypic adaptation of this cell type, we investigated patterns of monocyte gene expression in circulating monocytes at various stages of MI. Circulating monocytes were isolated from venous blood of MI patients at three time points: t1: within 6 hours after onset of chest pain (acute phase), t2: 3 days after MI (subacute phase), t3: 90 days after MI (chronic phase). For comparison, we studied a control group (n=21, data to be submitted later) with stable coronary artery disease. Illumina Ref-8 v3.0 microarray arrays were used for whole-genome transcriptional profiling.
2012-04-30 | E-GEOD-28454 | biostudies-arrayexpress