Iacobas Dumitru A, Allen Haile, Iacobas Sanda
Undergraduate Medical Academy, Prairie View A&M University, Prairie View, TX 77446, USA.
Department of Pathology, New York Medical College, Valhalla, NY 10595, USA.
Curr Issues Mol Biol. 2024 Mar 12;46(3):2355-2385. doi: 10.3390/cimb46030150.
Low-salt diet (LSD) is a constant recommendation to hypertensive patients, but the genomic mechanisms through which it improves cardiac pathophysiology are still not fully understood. Our publicly accessible transcriptomic dataset of the left ventricle myocardium of adult male mice subjected to prolonged LSD or normal diet was analyzed from the perspective of the Genomic Fabric Paradigm. We found that LSD shifted the metabolic priorities by increasing the transcription control for fatty acids biosynthesis while decreasing it for steroid hormone biosynthesis. Moreover, LSD remodeled pathways responsible for cardiac muscle contraction (CMC), chronic Chagas (CHA), diabetic (DIA), dilated (DIL), and hypertrophic (HCM) cardiomyopathies, and their interplays with the glycolysis/glucogenesis (GLY), oxidative phosphorylation (OXP), and adrenergic signaling in cardiomyocytes (ASC). For instance, the statistically ( < 0.05) significant coupling between GLY and ASC was reduced by LSD from 13.82% to 2.91% (i.e., -4.75×), and that of ASC with HCM from 10.50% to 2.83% (-3.71×). The substantial up-regulation of the CMC, ASC, and OXP genes, and the significant weakening of the synchronization of the expression of the HCM, CHA, DIA, and DIL genes within their respective fabrics justify the benefits of the LSD recommendation.
低盐饮食(LSD)一直是高血压患者的建议,但它改善心脏病理生理学的基因组机制仍未完全了解。我们从基因组结构范式的角度分析了成年雄性小鼠左心室心肌的公开转录组数据集,这些小鼠接受了长期的低盐饮食或正常饮食。我们发现,低盐饮食通过增加脂肪酸生物合成的转录控制,同时减少类固醇激素生物合成的转录控制,改变了代谢优先级。此外,低盐饮食重塑了负责心肌收缩(CMC)、慢性恰加斯病(CHA)、糖尿病(DIA)、扩张型(DIL)和肥厚型(HCM)心肌病的途径,以及它们与心肌细胞中糖酵解/糖异生(GLY)、氧化磷酸化(OXP)和肾上腺素能信号传导(ASC)的相互作用。例如,低盐饮食使GLY和ASC之间的统计学显著耦合(<0.05)从13.82%降至2.91%(即-4.75倍),ASC与HCM之间的耦合从10.50%降至2.83%(-3.71倍)。CMC、ASC和OXP基因的大量上调,以及HCM、CHA、DIA和DIL基因在各自结构内表达同步性的显著减弱,证明了低盐饮食建议的益处。