Mohr Alex E, Reiss Rebecca A, Beaudet Monique, Sena Johnny, Naik Jay S, Walker Benjimen R, Sweazea Karen L
College of Health Solutions, Arizona State University, Phoenix, AZ, United States.
Biology Department, New Mexico Institute of Mining and Technology, Socorro, NM, United States.
PeerJ. 2021 Jul 9;9:e11714. doi: 10.7717/peerj.11714. eCollection 2021.
Diet-induced metabolic dysfunction precedes multiple disease states including diabetes, heart disease, and vascular dysfunction. The critical role of the vasculature in disease progression is established, yet the details of how gene expression changes in early cardiovascular disease remain an enigma. The objective of the current pilot project was to evaluate whether a quantitative assessment of gene expression within the aorta of six-week old healthy male Sprague-Dawley rats compared to those exhibiting symptoms of metabolic dysfunction could reveal potential mediators of vascular dysfunction.
RNA was extracted from the aorta of eight rats from a larger experiment; four animals fed a high-fat diet (HFD) known to induce symptoms of metabolic dysfunction (hypertension, increased adiposity, fasting hyperglycemia) and four age-matched healthy animals fed a standard chow diet (CHOW). The bioinformatic workflow included Gene Ontology (GO) biological process enrichment and network analyses.
The resulting network contained genes relevant to physiological processes including fat and protein metabolism, oxygen transport, hormone regulation, vascular regulation, thermoregulation, and circadian rhythm. The majority of differentially regulated genes were downregulated, including several associated with circadian clock function. In contrast, leptin and 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) were notably upregulated. Leptin is involved in several major energy balance signaling pathways and Hmgcs2 is a mitochondrial enzyme that catalyzes the first reaction of ketogenesis.
Together, these data describe changes in gene expression within the aortic wall of HFD rats with early metabolic dysfunction and highlight potential pathways and signaling intermediates that may impact the development of early vascular dysfunction.
饮食诱导的代谢功能障碍先于多种疾病状态出现，包括糖尿病、心脏病和血管功能障碍。血管系统在疾病进展中的关键作用已得到确立，但早期心血管疾病中基因表达变化的细节仍是一个谜。当前试点项目的目的是评估与表现出代谢功能障碍症状的六周龄健康雄性Sprague-Dawley大鼠相比，对其主动脉内基因表达进行定量评估是否能揭示血管功能障碍的潜在介质。
从一项更大规模实验的八只大鼠的主动脉中提取RNA；四只动物喂食已知会诱发代谢功能障碍症状（高血压、肥胖增加、空腹血糖升高）的高脂饮食（HFD），另外四只年龄匹配的健康动物喂食标准饲料（CHOW）。生物信息学工作流程包括基因本体（GO）生物学过程富集和网络分析。
生成的网络包含与生理过程相关的基因，包括脂肪和蛋白质代谢、氧气运输、激素调节、血管调节、体温调节和昼夜节律。大多数差异调节基因被下调，包括几个与昼夜节律钟功能相关的基因。相比之下，瘦素和3-羟基-3-甲基戊二酰辅酶A合酶2（Hmgcs2）显著上调。瘦素参与多个主要的能量平衡信号通路，Hmgcs2是一种线粒体酶，催化生酮作用的第一步反应。
总之，这些数据描述了早期代谢功能障碍的高脂饮食大鼠主动脉壁内基因表达的变化，并突出了可能影响早期血管功能障碍发展的潜在途径和信号中间体。
