Matshazi Don M, Weale Cecil J, Erasmus Rajiv T, Kengne Andre P, Davids Saarah F G, Raghubeer Shanel, Hector Stanton, Davison Glenda M, Matsha Tandi E
South African Medical Research Council/Cape Peninsula University of Technology Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa.
Division of Chemical Pathology, Faculty of Health Sciences, National Health Laboratory Service and Stellenbosch University, Cape Town, South Africa.
Front Cardiovasc Med. 2021 Apr 16;8:645541. doi: 10.3389/fcvm.2021.645541. eCollection 2021.
Hypertension has a complex pathogenesis and symptoms appear in advanced disease. Dysregulation of gene expression regulatory factors like microRNAs has been reported in disease development. Identifying biomarkers which could help understand the pathogenesis and prognosis of hypertension is essential. The study's objective was to investigate microRNA expression profiles according to participant blood pressure status. Next generation sequencing was used to identify microRNAs in the whole blood of 48 body mass index-, smoking- and age-matched normotensive ( = 12), screen-detected hypertensive ( = 16) and known hypertensive ( = 20) female participants. Quantitative reverse transcription polymerase chain reaction was used to validate the next generation sequencing findings in a larger, independent sample of 84 men and 179 women. Using next generation sequencing, 30 dysregulated microRNAs were identified and miR-1299 and miR-30a-5p were the most significantly differentially expressed. Both microRNAs were upregulated in known hypertensives or screen-detected hypertensives compared to the normotensives. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated possible involvement of platelet activation, calcium signaling and aldosterone synthesis pathways. Further validation of miR-1299 and miR-30a-5p using quantitative reverse transcription polymerase chain reaction confirmed sequencing results while yielding new findings. These findings demonstrate microRNA dysregulation in hypertension and their expression may be related to genes and biological pathways essential for blood pressure homeostasis.
高血压具有复杂的发病机制,症状出现在疾病晚期。据报道,微小RNA等基因表达调控因子的失调在疾病发展过程中存在。识别有助于理解高血压发病机制和预后的生物标志物至关重要。该研究的目的是根据参与者的血压状况调查微小RNA表达谱。采用新一代测序技术,在48名体重指数、吸烟状况和年龄匹配的女性参与者中,分别选取12名血压正常者、16名筛查发现的高血压患者和20名已知高血压患者,对其全血中的微小RNA进行鉴定。采用定量逆转录聚合酶链反应,在一个由84名男性和179名女性组成的更大的独立样本中验证新一代测序结果。通过新一代测序,鉴定出30种失调的微小RNA,其中miR-1299和miR-30a-5p差异表达最为显著。与血压正常者相比,已知高血压患者或筛查发现的高血压患者中这两种微小RNA均上调。京都基因与基因组百科全书通路富集分析表明,血小板活化、钙信号传导和醛固酮合成通路可能参与其中。使用定量逆转录聚合酶链反应对miR-1299和miR-30a-5p进行进一步验证,证实了测序结果,同时得出了新的发现。这些发现表明高血压中存在微小RNA失调,其表达可能与血压稳态所必需的基因和生物学通路有关。