Gu Wei, Liu Jielin, Liu Ya, Wang Zuoguang
Coronary Heart Disease Center, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Department of Hypertension Research, Beijing Anzhen Hospital, Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
Hypertens Res. 2025 Apr 16. doi: 10.1038/s41440-025-02200-4.
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.
高血压是一种复杂的疾病，受遗传易感性、神经和内分泌失调、心血管和肾功能障碍以及不健康生活方式的影响。它是许多疾病的主要危险因素。然而，迄今为止，高血压潜在的病理生理机制尚未得到系统的描述。在本研究中，我们使用RNA测序比较了自发性高血压大鼠（SHR）和Wistar Kyoto（WKY，对照品系）模型之间的生理和分子变化。与WKY对照大鼠相比，SHR模型在3至15周内血压显著升高。此外，超声心动图和免疫组织化学分析显示SHR中心脏重塑和纤维化指标升高。RNA测序结果揭示了SHR和WKY每周之间差异表达的基因，这些基因与爱泼斯坦-巴尔病毒感染失调、流体切应力和动脉粥样硬化、RNA降解以及内分泌抵抗有关。转录组分析表明，与高血压相关的差异表达基因参与了缺氧诱导因子-1（HIF-1）和白细胞介素-17（IL-17）信号通路。此外，基因本体（GO）功能分析表明，差异表达基因主要与催化活性和蛋白质结合相关。维恩图分析确定KCNE1、Lad1、SLC9A3和Frzb为高血压的潜在靶点。此外，这四个基因的表达表现出优异的敏感性和特异性，表明它们在高血压诊断中的潜在效用。这些发现为理解高血压及相关心脏重塑提供了理论基础。
