Dataset Information

Upregulated microRNA?330?3p promotes calcification in the bicuspid aortic valve via targeting CREBBP.

ABSTRACT: One key risk factor of aortic valve stenosis in clinical practice is bicuspid aortic valve (BAV). Increasing evidence indicates that numerous microRNAs (miRs/miRNAs) are involved in BAV calcification via their target genes. miR?330?3p was found to be involved in the deterioration of BAV calcification by miR profiling in human calcified BAV and tricuspid aortic valve (TAV) tissues in the present study and the underlying mechanism was investigated. RNA sequencing was performed on four BAV and four TAV tissues from patients with aortic stenosis before these leaflets were examined for the expression levels of miR?330?3p and CREB?binding protein (CREBBP) by reverse transcription?PCR. The alteration of functional factors associated with calcification was also assessed by Western blotting and immunohistochemistry in human aortic tissue samples. The putative target of miR?330?3p was detected by dual?luciferase assay in 293 cells. Furthermore, the influence of miR?330?3p expression on osteogenic progression was explored in cultured porcine valve interstitial cells (VICs). Rescue experiments of CRBBP were performed to confirm the influence of the miR?330?3p?CREBBP pathway in the calcification progress in porcine VICs. RNA sequencing indicated distinct expression of miR?330?3p in human BAV tissues compared with TAV, which was then confirmed by PCR. CREBBP expression levels in human BAV and TAV leaflets also demonstrated the opposite alterations. This negative correlation was then confirmed in cultured porcine VICs. Under an osteogenic environment, cellular calcification was promoted in miR?330?3p?overexpressed porcine VICs expressing higher bone morphogenetic protein 2, Runt?related transcription factor 2, matrix metalloproteinase (MMP)?2, MMP?9 and collagen I compared with controls. Rescue experiments further confirmed that miR?330?3p played its role via targeting CREBBP in porcine VICs. Collectively, miR?330?3p was upregulated in calcified BAV compared with TAV. The upregulation of miR?330?3p promotes the calcification progress partially via targeting CREBBP.

SUBMITTER: Zheng R

PROVIDER: S-EPMC7411470 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Upregulated microRNA‑330‑3p promotes calcification in the bicuspid aortic valve via targeting CREBBP.

Zheng Rui R Liu Hao H Gu Jiaxi J Ni Buqing B Sun Haoliang H Guo Yaojun Y Su Chen C He Keshuai K Du Junjie J Shao Yongfeng Y

Molecular medicine reports 20200706 3

One key risk factor of aortic valve stenosis in clinical practice is bicuspid aortic valve (BAV). Increasing evidence indicates that numerous microRNAs (miRs/miRNAs) are involved in BAV calcification via their target genes. miR‑330‑3p was found to be involved in the deterioration of BAV calcification by miR profiling in human calcified BAV and tricuspid aortic valve (TAV) tissues in the present study and the underlying mechanism was investigated. RNA sequencing was performed on four BAV and four ...[more]

PMID: 32705274

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Project description:ImportanceThe outcomes of transcatheter aortic valve replacement (TAVR) in low-risk patients with bicuspid aortic valve stenosis have not been studied in a large scale, multicentered, prospective fashion.ObjectiveTo evaluate the procedural safety, efficacy, and 30-day outcomes of TAVR in patients with bicuspid aortic stenosis at low surgical risk.Design, setting, and participantsThe Low Risk Bicuspid Study is a prospective, single-arm trial study with inclusion/exclusion criteria developed from the Evolut Low Risk Randomized Trial. Follow-up is planned for 10 years. Patients underwent TAVR at 25 centers in the United States who were also participating in the Evolut Low Risk Randomized Trial from December 2018 to October 2019. Eligible patients had severe bicuspid aortic valve stenosis and met American Heart Association/American College of Cardiology guideline indications for aortic valve replacement.InterventionsPatients underwent attempted implant of an Evolut or Evolut PRO transcatheter aortic valve, with valve size based on annular measurements.Main outcomes and measuresThe prespecified primary end point was the incidence of all-cause mortality or disabling stroke at 30 days. The prespecified primary efficacy end point was device success defined as the absence of procedural mortality, the correct position of 1 bioprosthetic heart valve in the proper anatomical location, and the absence of more than mild aortic regurgitation postprocedure.ResultsA total of 150 patients underwent an attempted implant. Baseline characteristics include mean age of 70.3 (5.5) years, 48.0% female (n = 72), and a mean Society of Thoracic Surgeons score of 1.4 (0.6%). Most patients (136; 90.7%) had Sievers type I valve morphology. The incidence of all-cause mortality or disabling stroke was 1.3% (95% CI, 0.3%-5.3%) at 30 days. The device success rate was 95.3% (95% CI, 90.5%-98.1%). At 30 days, the mean (SD) AV gradient was 7.6 (3.7) mm Hg and effective orifice area was 2.3 (0.7) cm2. A new permanent pacemaker was implanted in 22 patients (15.1%). No patients had greater than mild paravalvular leak.Conclusions and relevanceTranscatheter aortic valve replacement in low-surgical risk patients with bicuspid aortic valve stenosis achieved favorable 30-day results, with low rates of death and stroke and high device success rate.Trial registrationClinicalTrials.gov Identifier: NCT03635424.

Dataset Information

Upregulated microRNA?330?3p promotes calcification in the bicuspid aortic valve via targeting CREBBP.

Publications

Upregulated microRNA‑330‑3p promotes calcification in the bicuspid aortic valve via targeting CREBBP.

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