Division of Nephrology and Hypertension Henry Ford Health Detroit MI.
Division of Nephrology and Hypertension Wayne State University Detroit MI.
J Am Heart Assoc. 2023 Mar 21;12(6):e026242. doi: 10.1161/JAHA.122.026242. Epub 2023 Mar 9.
Background The renal mechanisms involved in the maintenance of human hypertension and resistance to treatment are not well understood. Animal studies suggest that chronic renal inflammation contributes to hypertension. We studied cells shed in first-morning urine samples from individuals who were hypertensive who exhibited difficult-to-control blood pressure (BP). We performed bulk RNA sequencing of these shed cells to develop transcriptome-wide associations with BP. We also analyzed nephron-specific genes and used an unbiased bioinformatic approach to find signaling pathways activated in difficult-to-control hypertension. Methods and Results Participants who completed the SPRINT (Systolic Blood Pressure Intervention Trial) at a single trial site were recruited, and cells shed in first-morning urine samples collected. A total of 47 participants were divided into 2 groups based on hypertension control. The BP-difficult group (n=29) had systolic BP>140 mm Hg, >120 mm Hg after intensive treatment for hypertension, or required more than the median number of antihypertensive drugs used in SPRINT. The easy-to-control BP group (n=18) comprised the remainder of the participants. A total of 60 differentially expressed genes were identified with a >2-fold change in the BP-difficult group. In BP-difficult participants, 2 of the most upregulated genes were associated with inflammation: Tumor Necrosis Factor Alpha Induced Protien 6 (fold change, 7.76; =0.006) and Serpin Family B Member 9 (fold change, 5.10; =0.007). Biological pathway analysis revealed an overrepresentation of inflammatory networks, including interferon signaling, granulocyte adhesion and diapedesis, and Janus Kinase family kinases in the BP-difficult group (<0.001). Conclusions We conclude that transcriptomes from cells shed in first-morning urine identify a gene expression profile in difficult-to-control hypertension that associates with renal inflammation.
背景 人类高血压和治疗抵抗的肾脏机制尚不清楚。动物研究表明，慢性肾炎症有助于高血压。我们研究了来自高血压患者晨尿样本中脱落的细胞，这些患者血压难以控制。我们对这些脱落细胞进行了大量 RNA 测序，以开发与血压相关的转录组关联。我们还分析了肾单位特异性基因，并使用无偏生物信息学方法寻找在难以控制的高血压中激活的信号通路。
方法和结果 在一个单一试验点完成 SPRINT（收缩压干预试验）的参与者被招募，并收集晨尿样本中脱落的细胞。共有 47 名参与者根据高血压控制情况分为 2 组。BP 困难组（n=29）的收缩压>140mmHg，强化降压治疗后>120mmHg，或需要使用 SPRINT 中使用的降压药物中位数以上。容易控制 BP 组（n=18）由其余参与者组成。BP 困难组有 60 个差异表达基因，表达变化>2 倍。在 BP 困难组中，上调最明显的 2 个基因与炎症有关：肿瘤坏死因子-α诱导蛋白 6（fold change，7.76；=0.006）和 Serpin 家族 B 成员 9（fold change，5.10；=0.007）。生物途径分析显示，BP 困难组中炎症网络、干扰素信号、粒细胞黏附和渗出以及 Janus 激酶家族激酶过度表达（<0.001）。
结论 我们得出结论，晨尿中脱落细胞的转录组可识别出难以控制的高血压中与肾脏炎症相关的基因表达谱。
