Abstract
OBJECTIVES:Diagnosis and management of essential hypertension (EH) or type 2 diabetes mellitus (T2DM) by combining comprehensive treatment and classificatory diagnosis have been continuously improved. However, understanding the pathogenesis of EH patients with concomitant T2DM and subsequent treatment remain the major challenges owing to the lack of non-invasive biomarkers and information regarding the underlying mechanisms.METHODS:Herein, we collected 200 serum samples from EH and/or T2DM patients and healthy donors (N). Gene-expression profiling was conducted to identify candidate microRNAs with clinical significance. Then, a larger cohort of the aforementioned patients and 50 N were used to identify the correlation between the tumor suppressor miR-195-5p and EH and/or T2DM. The dual-luciferase reporter assay was used to explore the target genes of miR-195-5p. The suppressive effects of miR-195-5p on the 3′-UTR of the dopamine receptor D1 (DRD1) transcript in EH patients with concomitant T2DM were verified as well.RESULTS:Compared with that in other groups, serum miR-195-5p was highly downregulated in EH patients with concomitant T2DM. miR-195-5p overexpression efficiently suppressed DRD1 expression by binding to the two 3′-UTRs. Additionally, two single nucleotide polymorphisms, including 231T-A and 233C-G, in the miR-195-5p binding sites of the DRD1 3′-UTR were further identified. Collectively, we identified the potential clinical significance of DRD1 regulation by miR-195-5p in EH patients with concomitant T2DM.CONCLUSIONS:Our data suggested that miR-195-5p circulating in the peripheral blood served as a novel biomarker and therapeutic target for EH and T2DM, which could eventually help address major challenges during the diagnosis and treatment of EH and T2DM.
Highlights
Multiple parameters, such as body mass index (BMI), fasting bloodglucose (FBG), low density lipoprotein cholesterin (LDL-C), and high density lipoprotein cholesterol (HDL-C) in the N group were different from those in E with D (ED) patients, differences occurred among E, D and ED patients (Figures 1BÀ1F)
Our research revealed that serum miR-195-5p exhibits clinical significance with respect to non-invasive diagnosis and interventional therapeutics and provides insights into the pathogenesis of Essential hypertension (EH) with type 2 diabetes mellitus (T2DM)
In this study we identified serum miR-195-5p as a novel non-invasive biomarker for clinical diagnosis and interventional therapeutics for EH with concomitant T2DM that functions by by directly suppressing dopamine receptor D1 (DRD1) expression
Summary
Essential hypertension (EH)—defined as the unexplained rise in blood pressure—is a major cause of cardiovascular and cerebrovascular diseases with a worldwide prevalence ranging from 26.4% in 2000 to 29.2% in 2025 that is mainly. Longitudinal studies have indicated the involvement and clusters of predisposing factors, such as being overweight, the aging process, hyperlipidemia, and insulin resistance-associated type 2 diabetes mellitus (T2DM), yet the precise pathogenesis of EH requires further understanding [2,3]. Multifaceted T2DM and/or complication-associated inducements, such as hyperglycemia, insulin resistance, excess fatty acids, and the malfunction of pancreatic beta cells are sufficient for inducing thrombosis, vasoconstriction, vascular inflammation, and atherogenesis, which collectively result in the development of EH-associated cardiovascular diseases [3,4,5]. More than 39% of the patients with newly diagnosed T2DM were more hypertensive than normotensive patients, whereas EH occurred in up to 75% of the adult T2DM miR-195-5p in EH patients with T2DM Hu Y et al
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