New Insights into the Role of HMGB2 in ST-Segment Elevation Myocardial Infarction
Hao Qin1, Wenjun Wang2, Longlong Hu1
1Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
Insights
High mobility group box 2 (HMGB2) is elevated in ST-segment elevation myocardial infarction (STEMI) patients, promoting platelet activation. This suggests HMGB2 may be a therapeutic target for STEMI, a leading cause of death.
Area of Science:
- Cardiovascular Biology
- Hematology
- Molecular Medicine
Background:
- Ischemic heart disease, including ST-segment elevation myocardial infarction (STEMI), is a major global cause of mortality.
- Platelet activation and aggregation are critical in the thrombosis leading to acute vessel occlusion in STEMI.
- The role of high mobility group box 2 (HMGB2) in platelet activation remains largely uncharacterized.
Purpose of the Study:
- To investigate the role of HMGB2 in platelet activation in patients with STEMI.
- To identify potential molecular mechanisms linking HMGB2 to STEMI pathogenesis.
Main Methods:
- Proteomic analysis of platelets from STEMI patients and healthy controls using mass spectrometry.
- Differential expression analysis to identify key proteins, including HMGB2.
- Validation of HMGB2 expression via Western blot and ELISA.
- Assessment of platelet activation markers and aggregation in response to recombinant HMGB2 (rHMGB2).
Main Results:
- HMGB2 was identified as a significantly upregulated protein in platelets of STEMI patients.
- Serum HMGB2 levels were elevated in STEMI patients and correlated with neutrophil count.
- Recombinant HMGB2 enhanced platelet aggregation, integrin αIIbβ3 activation, and CD62P expression.
Conclusions:
- HMGB2 plays a significant role in regulating platelet activation in STEMI.
- HMGB2 represents a potential therapeutic target for managing STEMI.
Background:
Ischemic heart disease is one of the leading causes of death in the world, of which ST-segment elevation myocardial infarction (STEMI) is an important type. Inappropriate activation and accumulation of platelets typically induced thrombosis, which may result in acute vessel occlusion and STEMI. Multiple cytokines have been shown to regulate platelet activation, but the relationship between HMGB2 and platelet activation has not been elucidated.
Methods:
We collected peripheral blood of STEMI patients and healthy adults, and mass spectrometry analysis of platelet proteins was conducted. The "edgeR" package was used to identify the differentially expressed proteins (DEPs). The Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene ontology (GO) and Gene Set Enrichment Analysis (GSEA) were used to identify the significantly changed pathways. Western blot and ELISA were used to detect the expression of a high mobility group box 2 (HMGB2). Flow cytometric analysis and platelet aggregation rate were performed to evaluate the activation of platelets.
Results:
We identified ALOX5, HIST1H1B, S100A11, HMGB2, and RPS15A were the top five up-regulated proteins by differential expression analysis. Western blot verified that the relative protein expression of HMGB2 in platelet was significantly higher in STEMI patients compared with control adults, and the results of ELISA indicated that the serum HMGB2 level increased and significantly correlated with neutrophil count in STEMI patients. Further investigation showed that the platelet aggregation induced by ADP, the activation of integrin αIIbβ3 and CD62P expression on platelet surface were all enhanced by the recombinant HMGB2 (rHMGB2).
Conclusion:
In conclusion, HMGB2 may be the key molecule to regulate platelet activation in patients with STEMI, which may serve as a potential therapeutic target for STEMI.
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