Identification of potential biomarkers for hypertension based on transcriptomic analysis in rats

Hypertension is a complex disorder influenced by genetic predisposition, neural and endocrine dysregulation, cardiovascular and renal dysfunction, and unhealthy lifestyles. It is a major risk factor for many diseases. However, the pathophysiological mechanisms underlying hypertension have not been systematically characterized to date. In this study, we compared physiological and molecular changes between spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY, control strain) models using RNA sequencing. Blood pressure increased significantly in SHR models over 3-15 weeks compared with WKY control rats. Furthermore, indicators of cardiac remodeling and fibrosis were elevated in SHR on echocardiography and immunohistochemical analyses. RNA sequencing findings revealed differentially expressed genes between SHRs and WKYs in each week, which were related to dysregulation of Epstein-Barr virus infection, fluid shear stress and atherosclerosis, RNA degradation, and endocrine resistance. Transcriptome analysis showed that differentially expressed genes related to hypertension were involved in the hypoxia inducible factor-1 (HIF-1) and interleukin-17 (IL-17) signaling pathways. Furthermore, Gene Ontology (GO) functional analysis showed that differentially expressed genes were mainly associated with catalytic activity and protein binding. The Venn diagram analysis identified KCNE1, Lad1, SLC9A3, and Frzb as potential targets of hypertension. In addition, the expression of these four genes exhibited excellent sensitivity and specificity, suggesting their potential diagnostic utility in hypertension. These findings support a theoretical basis for understanding hypertension and related heart remodeling.