Genes representing the stress-dependent component in arterial hypertension development

Area of Science:

• Molecular Biology
• Genetics
• Cardiovascular Research

Background:

• Hypertension is a major cardiovascular disease risk factor.
• Chronic psychoemotional stress is a key cause of hypertension.
• Animal models, like the ISIAH and WAG rats, are crucial for studying hypertension's molecular mechanisms.

Purpose of the Study:

• To investigate the shared molecular mechanisms between psychoemotional stress and hypertension.
• To identify potential diagnostic markers for psychoemotional stress.

Main Methods:

• Utilized the RatDEGdb database for hypothalamic gene expression in hypertensive and normotensive rats under stress.
• Annotated rat genes with human orthologs using differential gene expression (DEG) data from hypertensive patients.
• Applied principal component analysis (PCA) to orthologous DEGs from rats and humans.

Main Results:

• PCA revealed that two components explained 64% and 33% of gene expression variance, linking stress response in rats to human hypertension.
• A significant correlation between stress-induced gene downregulation and hypertension suggests shared molecular pathways.
• Downregulation of genes related to plasma membrane and extracellular matrix interactions, mediated by the SMARCA4 transcription factor, is implicated in stress-induced hypertension.

Conclusions:

• Psychoemotional stress and hypertension share common molecular mechanisms, particularly involving stress-induced gene downregulation.
• The SMARCA4 transcription factor may mediate epigenetic modifications contributing to hypertension under chronic stress.
• Peripheral blood markers for diagnosing psychoemotional stress are proposed, offering potential diagnostic tools.