Genes representing the stress-dependent component in arterial hypertension development

Hypertension is among the major risk factors of many cardiovascular diseases. Chronic psychoemotional stress is one of its key causes. Studies of molecular mechanisms of human hypertension development are conducted in animals, including artificial rat strains that model various forms of the disease. The RatDEGdb database, used in our work, includes 144 hypothalamic genes that represent the common response to single short-term restraint stress in hypertensive ISIAH and normotensive WAG rats. These rat genes were annotated with changes in the expression of the human orthologs using data on 17,458 differentially expressed genes (DEGs) from patients with hypertension compared to normotensive subjects. We applied principal component analysis to orthologous pairs of DEGs identified in hypertensive patients and rat hypothalamic DEGs upon single short-term restraint stress. Two principal components, corresponding to a linear combination of log2 expression changes associated with the similarity (PC1) and difference (PC2) in the response to psychoemotional stress in two rat strains, on the one hand, and different forms of human hypertension, on the other, explained 64 % and 33 % of the variance in differential gene expression, respectively. The significant correlation revealed between PC1 and PC2 values for the group of DEGs with stress-induced downregulation indicates that psychoemotional stress and hypertension share a common molecular mechanism. Functional annotation suggests that stress-induced downregulation of genes involved in the plasma membrane function and, simultaneously, interactions with the extracellular matrix is the most likely contribution of psychoemotional stress to the development of the hypertensive status inpatients, and the SMARCA4 transcription factor is the most likely mediator in the epigenetic modification affecting gene expression under chronic stress. Peripheral blood markers for the diagnosis of psychoemotional stress are proposed. 

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