Beta3 adrenergic receptor is involved in vascular injury in deoxycorticosterone acetate‐salt hypertensive mice

Lijuan, Sheng; Ruan, Chun; Ma, Yu; Chen, Dong-Rui; Kong, Lingrang; Zhu, Dongsheng; Gao, Pingjin

doi:10.1002/1873-3468.12107

Cited by 17 publications

(11 citation statements)

References 17 publications

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“…Significant upregulated expression of let-7b and miR-144 in T2DM patients in our study may indicates downregulated expression of their target gene, including ADBR2/ADBR3 (β-adrenoreceptors) and NR3C1 (GR), respectively. Sheng, et al verified that the protein expression of ADRB3 was regulated by direct binding of let-7b at 3′-UTR ( 22 ). In addition, they found that let-7b was negatively correlated with ADRB3 protein level and had a decreased expression in perivascular adipose tissue of hypertensive mice.…”

Section: Discussionmentioning

confidence: 99%

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Identification of Neuroendocrine Stress Response-Related Circulating MicroRNAs as Biomarkers for Type 2 Diabetes Mellitus and Insulin Resistance

et al. 2018

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BackgroundChronic stress plays an important role in the development of type 2 diabetes mellitus (T2DM) and insulin resistance (IR). MicroRNAs (miRNAs) play key roles in mediating stress responses by regulating the expression of target genes. This study systematically screened and identified the neuroendocrine stress response-related circulating miRNAs which are associated with T2DM and IR.MethodsBased on the differential plasma expression profiles between individuals with and without T2DM, stress-related miRNAs were selected from those differently expressed miRNAs whose targets are involved in known neuroendocrine pathway of stress response. Candidate miRNAs were further validated by quantitative real-time polymerase chain reaction in a large sample, including 112 T2DM patients, 72 individuals with impaired fasting glucose (IFG), and 94 healthy controls. The association between miRNA expression and potential risk of T2DM and IFG was assessed by multivariate logistic regression models. The miRNA predictors of IR were identified by stepwise multiple regression analysis. The diagnostic performance for T2DM was evaluated by area under the curve (AUC) of receiver operating characteristic (ROC).Resultslet-7b, let-7i, miR-142, miR-144, miR-155, and miR-29a were selected as candidate miRNAs for validation. Increased expression of let-7b, miR-144, and miR-29a and decreased expression of miR-142 were significant independent predictors of T2DM, IFG, and IR (P < 0.0125). These miRNAs significantly correlated with stress hormone levels (P < 0.0125). A three-miRNA panel, including let-7b, miR-142, and miR-144 had a high accuracy for diagnosing T2DM (AUC = 0.871, 95% CI: 0.822–0.919).Conclusionlet-7b, miR-142, miR-144, and miR-29a in plasma may be important markers of neuroendocrine stress response and may play a role in the pathogenesis of T2DM and IR.

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Section: Discussionmentioning

confidence: 99%

“…Both plasma CRH and IL-6 were negatively associated with miR-142 expression in total subjects, which may be explained by the inhibitory effect of miRNA on target genes. Microarray analysis revealed the downregulation miR-142 in the peripheral blood of mice associated with pronounced enhanced oxidative stress ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Neuroendocrine Stress Response-Related Circulating MicroRNAs as Biomarkers for Type 2 Diabetes Mellitus and Insulin Resistance

et al. 2018

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“…Human β3-adrenoreceptor is a member of the family of 7-transmembrance G-protein-coupled receptors. It is widely recognized that the β3-adrenoreceptor is indirectly involved in the etiology of hypertension through reducing lipolysis and activating the sympathetic nervous system [ 25 , 32 ]. Numerous studies have suggested that hypertension is partly under genetic control, and therefore to look for candidate genetic markers responsible for hypertension predisposition and/or blood pressure changes is justifiable [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

The mutation of Trp64Arg in β3-adrenoreceptor-encoding gene is significantly associated with increased hypertension risk and elevated blood pressure: a meta-analysis

et al. 2017

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This meta-analysis was implemented to test the association of a missense mutation, Trp64Arg, in β3-adrenoreceptor-encoding gene (ADRB3) with both hypertension risk and blood pressure (BP) changes. A systematic search of three publicly-available databases was launched to look for articles published as of December 2016. Qualification appraisal and data extraction were independently done by two researchers. Pooled estimates were expressed as odds ratio (OR) or weighted mean difference (WMD), and their 95% confidence intervals (95% CIs). There were separately 21 (3750/4225 patients/controls) and 17 (6100 subjects) individual studies for hypertension risk and BP changes. Integral analyses revealed that Trp64Arg mutation was associated with the significantly increased risk of hypertension, and particularly, the 64Trp/64Arg heterozygote carriers were 1.23-times more likely to develop hypertension compared with the 64Trp/64Trp homozygote carriers (OR = 1.23, 95% CI: 1.02∼1.46, P = 0.021). Publication bias was extremely low for all integral comparisons. In stratified analyses, significance was spotted in populations of Chinese descent, in retrospective studies, in hospital-based studies, in age-matched case-control studies, in studies enrolling patients with mean body mass index < 25 kg/m2 and in studies with total sample size ≥ 240. Heterogeneity was improved for most stratified comparisons. Further in hypertensive patients, the 64Trp/64Arg heterozygote carriers had significantly higher systolic (WMD = 0.87 mmHg, 95% CI: 0.39∼1.35, P < 0.001) and diastolic (WMD = 0.88 mmHg, 95% CI: 0.59∼1.17, P < 0.001) BP than 64Trp/64Trp homozygote carriers. Altogether, ADRB3 gene Trp64Arg mutation was significantly associated with an increased predisposition toward hypertension and elevated systolic/diastolic BP in hypertensive patients, suggesting that Trp64Arg is an important hypertension-susceptibility marker.

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“…Systolic blood pressure was measured via a tail-cuff method using a non-invasive blood pressure instrument (BP-98A, Softron, China) at 3 days before and at 7 and 14 days after Ang II infusion as previously described (21).…”

Section: Methodsmentioning

confidence: 99%

Endothelial-specific deletion of Ets-1 attenuates Angiotensin II-induced cardiac fibrosis via suppression of endothelial-to-mesenchymal transition

Chen

et al. 2019

BMB Rep.

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Cardiac fibrosis is a common feature in chronic hypertension patients with advanced heart failure, and endothelial-to-mesenchymal transition (EndMT) is known to promote Angiotensin II (Ang II)-mediated cardiac fibrosis. Previous studies have suggested a potential role for the transcription factor, ETS-1, in Ang II-mediated cardiac remodeling, however the mechanism are not well defined. In this study, we found that mice with endothelial Ets-1 deletion showed reduced cardiac fibrosis and hypertrophy following Ang II infusion. The reduced cardiac fibrosis was accompanied by decreased expression of fibrotic matrix genes, reduced EndMT with decreased Snail, Slug, Twist, and ZEB1 expression, as well as reduced cardiac hypertrophy and expression of hypertrophy-associated genes was observed. In vitro studies using cultured H5V cells further confirmed that ETS-1 knockdown inhibited TGF-β1-induced EndMT. This study revealed that deletion of endothelial Ets-1 attenuated Ang II-induced cardiac fibrosis via inhibition of EndMT, indicating an important ETS-1 function in mediating EndMT. Inhibition of ETS-1 could be a potential therapeutic strategy for treatment of heart failure secondary to chronic hypertension.

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Beta3 adrenergic receptor is involved in vascular injury in deoxycorticosterone acetate‐salt hypertensive mice

Cited by 17 publications

References 17 publications

Identification of Neuroendocrine Stress Response-Related Circulating MicroRNAs as Biomarkers for Type 2 Diabetes Mellitus and Insulin Resistance

Identification of Neuroendocrine Stress Response-Related Circulating MicroRNAs as Biomarkers for Type 2 Diabetes Mellitus and Insulin Resistance

The mutation of Trp64Arg in β3-adrenoreceptor-encoding gene is significantly associated with increased hypertension risk and elevated blood pressure: a meta-analysis

Endothelial-specific deletion of Ets-1 attenuates Angiotensin II-induced cardiac fibrosis via suppression of endothelial-to-mesenchymal transition

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