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Published on: July 3, 2018
Myocardial Infarction Platelet Gene Expression Signatures in Women
Tessa J Barrett1, Florencia Schlamp1, Matthew Muller2
1New York University Grossman School of Medicine, New York, New York, USA; Sarah Ross Soter Center for Women's Cardiovascular Research, NYU Grossman School of Medicine, New York, New York, USA.
Insights
Platelets in women with myocardial infarction (MI) show altered gene expression acutely and chronically, impacting future cardiovascular events. These platelet signatures reveal distinct biological pathways and clinical features.
Area of Science:
- Cardiovascular Biology
- Platelet Genomics
- Transcriptomics
Background:
- Platelets are key in myocardial infarction (MI) pathogenesis.
- Limited data exists on female MI platelet transcriptomes, especially long-term.
- Understanding these changes is crucial for risk stratification and treatment.
Purpose of the Study:
- To characterize the MI platelet transcriptome in women during acute and chronic phases.
- To identify platelet gene expression patterns associated with future cardiovascular events.
- To compare platelet transcriptomes between MI with obstructive vs. non-obstructive coronary artery disease.
Main Methods:
- Transcriptomic analysis of platelets from women post-MI (acute and chronic) and controls.
- Analysis of an independent high-risk cohort to correlate gene expression with outcomes.
- Comparison of platelet gene expression in MI subgroups based on coronary artery disease severity.
Main Results:
- Acute MI platelets show enrichment in actin cytoskeleton, Rho GTPases, mitochondrial dysfunction, and inflammatory signaling.
- These transcriptomic changes persist chronically and are linked to future cardiovascular events.
- Women with obstructive coronary artery disease had platelets enriched in neutrophil activation and TNF-α signaling pathways compared to those with non-obstructive disease.
- Hierarchic clustering revealed three distinct MI patient subgroups based on transcriptomic profiles and clinical features.
Conclusions:
- Platelets exhibit distinct transcriptomic profiles in women with MI, both acutely and chronically.
- A specific platelet gene signature after MI is associated with increased risk of future cardiovascular events.
- Platelet transcriptomics can differentiate MI patient subgroups and may offer insights into disease mechanisms and clinical outcomes.
Abstract:
Although platelets play a critical pathogenic role in myocardial infarction (MI), few studies have characterized the MI platelet transcriptome in the acute or chronic setting in women. We report that transcripts associated with the actin cytoskeleton, Rho family GTPases, mitochondrial dysfunction, and inflammatory signaling are enriched in platelets from MI patients in the acute setting (n = 40, MI; n = 38, control) and do not significantly change over time. Furthermore, 79 platelet genes chronically elevated or suppressed after MI are associated with future cardiovascular events in an independent high-risk cohort (n = 135). Compared with women with MI with nonobstructive coronary arteries, platelets from women with MI and obstructive coronary artery disease were enriched in neutrophil activation and proinflammatory signaling pathways driven by increased tumor necrosis factor (TNF)-α signaling. Hierarchic clustering of the MI transcriptomic profile identified 3 subgroups with distinctive biological pathways and MI correlates. Our data demonstrate that platelets from MI patients are phenotypically different from MI-naïve patients in the acute and chronic settings and reveal a platelet transcriptomic signature with distinct clinical features.
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