Distinct transcriptomic profile of small arteries of hypertensive patients with chronic kidney disease identified miR-338-3p targeting GPX3 and PTPRS. Issue 7 (10th July 2022)

• Record Type: Journal Article
• Authors: Berillo, Olga; Huo, Ku-Geng; Richer, Chantal; Fraulob-Aquino, Júlio C.; Briet, Marie; Lipman, Mark L.; Sinnett, Daniel; Paradis, Pierre; Schiffrin, Ernesto L.
• Is Part Of: Journal of hypertension. Volume 40:Issue 7(2022)
• Page Start: 1394
• Page End: 1405
• Publication Date: 2022-07-10
• Subjects: end-organ damage -- hypertension -- RNA sequencing -- vascular injury; Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/HJH.0000000000003160
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objective: Hypertension is associated with vascular injury, which contributes to end-organ damage. MicroRNAs regulating mRNAs have been shown to play a role in vascular injury in hypertensive mice. We aimed to identify differentially expressed microRNAs and their mRNA targets in small arteries of hypertensive patients with/without chronic kidney disease (CKD) to shed light on the pathophysiological molecular mechanisms of vascular remodeling. Methods and results: Normotensive individuals and hypertensive patients with/without CKD were recruited ( n = 15–16 per group). Differentially expressed microRNAs and mRNAs were identified uniquely associated with hypertension (microRNAs: 10, mRNAs: 68) or CKD (microRNAs: 68, mRNAs: 395), and in both groups (microRNAs: 2, mRNAs: 32) with a P less than 0.05 and a fold change less than or greater than 1.3 in subcutaneous small arteries ( n = 14–15). One of the top three differentially expressed microRNAs, miR-338-3p that was down-regulated in CKD, presented the best correlation between RNA sequencing and reverse transcription-quantitative PCR (RT-qPCR, R 2 = 0.328, P < 0.001). Profiling of human aortic vascular cells showed that miR-338-3p was mostly expressed in endothelial cells. Two of the selected top nine up-regulated miR-338-3p predicted targets, glutathione peroxidase 3 ( GPX3 ) and protein tyrosine phosphatase receptor type S ( PTPRS ), were validated with mimics by RT-qPCR in human aortic endothelial cells ( P < 0.05) and by a luciferase assay in HEK293T cells ( P < 0.05). Conclusion: A distinct transcriptomic profile was observed in gluteal subcutaneous small arteries of hypertensive patients with CKD. Down-regulated miR-338-3p could contribute to GPX3 and PTPRS up-regulation via the canonical microRNA targeting machinery in hypertensive patients with CKD. Graphical abstract: http://links.lww.com/HJH/C27