Evolocumab Alters Transcriptomic Signatures and Identifies Inflammatory Biomarkers in Brain-Heart Syndrome with
Huijie Dong1, Xing Gong2, Zhenrong Zhao1
1Department of Cardiology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.
Insights
Evolocumab may help reduce inflammation in Brain-Heart Syndrome patients with coronary heart disease history. This study identified four potential inflammation biomarkers, WHRN, IL12A, ASB14, and TMED7-TICAM2, for future research.
Area of Science:
- Cardiovascular Medicine
- Neuroscience
- Pharmacogenomics
Background:
- Coronary heart disease (CHD) history elevates Brain-Heart Syndrome (BHS) risk post-stroke, linked to inflammation.
- Evolocumab, a PCSK9 inhibitor, possesses anti-inflammatory effects, but its transcriptomic impact in BHS patients with CHD is not well understood.
Purpose of the Study:
- To investigate the transcriptomic alterations induced by evolocumab in BHS patients with a history of CHD.
- To identify novel inflammation-related biomarkers associated with evolocumab treatment in this patient cohort.
Main Methods:
- Transcriptomic sequencing was performed on blood samples from 24 BHS patients with CHD history (rosuvastatin vs. rosuvastatin + evolocumab).
- Differential gene expression analysis and machine learning were employed to identify candidate biomarkers.
- Functional enrichment and immune infiltration analyses were conducted to understand pathway involvement.
Main Results:
- Four candidate biomarkers were identified: WHRN, IL12A, and ASB14 (upregulated) and TMED7-TICAM2 (downregulated) in the evolocumab group.
- Identified genes were enriched in cell metabolism, signal transduction, and immune regulation pathways.
- Modest changes in B-cell subsets were observed, with external validation confirming biomarker differential expression in coronary artery disease (CAD) patients.
Conclusions:
- This pilot study offers preliminary insights into evolocumab's molecular mechanisms in BHS with CHD, identifying four potential inflammation biomarkers.
- The findings suggest novel therapeutic targets for Brain-Heart Syndrome, warranting further clinical validation.
- Further research is essential to confirm these biomarkers and explore therapeutic applications due to the study's exploratory nature and small sample size.
Purpose:
A history of coronary heart disease (CHD) increases the risk of Brain-Heart Syndrome (BHS) after acute stroke, partly through heightened inflammatory responses. Evolocumab, a PCSK9 inhibitor, has anti-inflammatory properties, but its transcriptomic effects in BHS patients with CHD remain unclear. This study aims to identify evolocumab-associated transcriptomic changes and inflammation-related biomarkers in this population.
Patients And Methods:
Blood samples from 24 BHS patients with CHD history (12 receiving rosuvastatin alone, 12 receiving rosuvastatin plus evolocumab) underwent transcriptomic sequencing. Candidate biomarkers were identified via differential expression and machine learning, with functional enrichment and immune infiltration analyses conducted.
Results:
Four candidate biomarkers were identified: WHRN (DFNB31), IL12A, and ASB14 were upregulated, while TMED7-TICAM2 was downregulated in the evolocumab combination group. These genes were enriched in pathways related to cell metabolism, signal transduction, and immune regulation. Immune infiltration analysis showed modest but detectable changes in B-cell subsets. External validation confirmed differential expression of these candidate biomarkers in CAD patients.
Conclusion:
This pilot study provides preliminary insights into the molecular mechanisms of evolocumab in treating Brain-Heart Syndrome with a coronary heart disease history, identifying four inflammation-related biomarkers. These findings suggest potential targets for future investigation; however, given the exploratory nature and small sample size, further experimental and clinical validation is required before any therapeutic application.
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