Vargas Jose D, Abbas Malak, Goodney Gabriel, Gaye Amadou
DC Veteran affairs Medical Center, Washington, DC, USA.
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
bioRxiv. 2024 Aug 12:2024.08.11.607492. doi: 10.1101/2024.08.11.607492.
Arterial stiffness, commonly assessed via pulse wave velocity (PWV), is marked by reduced arterial elasticity and serves as a significant risk factor for cardiovascular disease and an early indicator of hypertension. This study investigated the regulatory roles of long non-coding RNAs (lncRNAs) in modulating mRNAs associated with arterial stiffness and hypertension, with a particular focus on African Americans, a population disproportionately impacted by hypertension.
We utilized whole-blood transcriptome sequencing data from two African American (AA) cohorts with high hypertension prevalence: the GENE-FORECAST study (436 subjects) and the MH-GRID study (179 subjects). Our objectives were to: (1) identify lncRNAs and mRNAs differentially expressed (DE) between the upper and lower tertiles of PWV, (2) determine DE lncRNAs associated with the expression levels of each DE mRNA, and (3) link the lncRNA-modulated mRNAs to hypertension across both datasets.
Differential expression analysis revealed 1,035 DE mRNAs and 31 DE lncRNAs between upper and lower PWV groups. Then lncRNA-mRNA pairs significantly associated were identified, involving 31 unique lncRNAs and 1,034 unique mRNAs. Finally, 22 of the lncRNA-modulated mRNAs initially linked to PWV were found associated with hypertension, in both datasets. Interestingly, 30 lncRNAs were linked to the expression of UCP2 (Uncoupling Protein 2), a gene implicated in oxidative stress and endothelial function.
Our findings underscore the significant roles of lncRNAs in regulating gene expression associated with arterial stiffness and hypertension. The differential expression of UCP2 in relation to PWV and hypertension, along with its potential regulation by lncRNAs, offers valuable insights into the molecular mechanisms underlying arterial stiffness and its connection with hypertension.
动脉僵硬度通常通过脉搏波速度（PWV）进行评估，其特征是动脉弹性降低，是心血管疾病的重要危险因素和高血压的早期指标。本研究调查了长链非编码RNA（lncRNA）在调节与动脉僵硬度和高血压相关的mRNA中的作用，特别关注非裔美国人，这是一个受高血压影响尤为严重的人群。
我们利用了来自两个高血压患病率高的非裔美国人（AA）队列的全血转录组测序数据：基因预测研究（436名受试者）和MH-GRID研究（179名受试者）。我们的目标是：（1）确定PWV上三分位数和下三分位数之间差异表达（DE）的lncRNA和mRNA，（2）确定与每个DE mRNA表达水平相关的DE lncRNA，以及（3）在两个数据集中将lncRNA调节的mRNA与高血压联系起来。
差异表达分析显示，PWV较高和较低组之间有1035个DE mRNA和31个DE lncRNA。然后鉴定出显著相关的lncRNA-mRNA对，涉及31个独特的lncRNA和1034个独特的mRNA。最后，在两个数据集中都发现，最初与PWV相关的22个lncRNA调节的mRNA与高血压有关。有趣的是，30个lncRNA与UCP2（解偶联蛋白2）的表达相关，UCP2是一个与氧化应激和内皮功能有关的基因。
我们的研究结果强调了lncRNA在调节与动脉僵硬度和高血压相关的基因表达中的重要作用。UCP2与PWV和高血压相关的差异表达，以及其可能受lncRNA调节，为动脉僵硬度的分子机制及其与高血压的联系提供了有价值的见解。
