Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad 44000, Pakistan.
Department of Pharmacy, Kohat University of Science and Technology, Kohat 26000, Pakistan.
Genes (Basel). 2022 Jan 21;13(2):187. doi: 10.3390/genes13020187.
Hypertension (HTN) is considered one of the most important and well-established reasons for cardiovascular abnormalities, strokes, and premature mortality globally. This study was designed to explore possible differentially expressed genes (DEGs) that contribute to the pathophysiology of hypertension. To identify the DEGs of HTN, we investigated 22 publicly available cDNA Affymetrix datasets using an integrated system-level framework. Gene Ontology (GO), pathway enrichment, and transcriptional factors were analyzed to reveal biological information. From 50 DEGs, we ranked 7 hypertension-related genes (-value < 0.05): ADM, ANGPTL4, USP8, EDN, NFIL3, MSR1, and CEBPD. The enriched terms revealed significant functional roles of HIF-1-α transcription; endothelin; GPCR-binding ligand; and signaling pathways of EGF, PIk3, and ARF6. SP1 (66.7%), KLF7 (33.3%), and STAT1 (16.7%) are transcriptional factors associated with the regulatory mechanism. The expression profiles of these DEGs as verified by qPCR showed 3-times higher fold changes (2-ΔΔCt) in ADM, ANGPTL4, USP8, and EDN1 genes compared to control, while CEBPD, MSR1 and NFIL3 were downregulated. The aberrant expression of these genes is associated with the pathophysiological development and cardiovascular abnormalities. This study will help to modulate the therapeutic strategies of hypertension.
高血压（HTN）被认为是全球心血管异常、中风和过早死亡最重要和最成熟的原因之一。本研究旨在探讨可能导致高血压病理生理学的差异表达基因（DEGs）。为了鉴定 HTN 的 DEGs，我们使用集成的系统水平框架研究了 22 个公开的 cDNA Affymetrix 数据集。进行基因本体论（GO）、通路富集和转录因子分析，以揭示生物学信息。从 50 个 DEGs 中，我们对 7 个与高血压相关的基因进行了排名（-值<0.05）：ADM、ANGPTL4、USP8、EDN、NFIL3、MSR1 和 CEBPD。富集术语揭示了 HIF-1-α转录、内皮素、GPCR 结合配体以及 EGF、PIk3 和 ARF6 信号通路的重要功能作用。SP1（66.7%）、KLF7（33.3%）和 STAT1（16.7%）是与调控机制相关的转录因子。qPCR 验证的这些 DEGs 的表达谱显示，与对照相比，ADM、ANGPTL4、USP8 和 EDN1 基因的倍数变化（2-ΔΔCt）高 3 倍，而 CEBPD、MSR1 和 NFIL3 下调。这些基因的异常表达与病理生理发展和心血管异常有关。本研究将有助于调节高血压的治疗策略。
