Dataset Information

MicroRNA-134-5p Regulates Media Degeneration through Inhibiting VSMC Phenotypic Switch and Migration in Thoracic Aortic Dissection.

ABSTRACT: Abnormal phenotypic switch, migration, and proliferation of vascular smooth muscle cells (VSMCs) are hallmarks for pathogenesis of thoracic aortic dissection (TAD). In the current study, we identified miR-134-5p as a critical regulator controlling human VSMC phenotypic switch and migration to investigate whether miR-134-5p affects human VSMC functions and development of TAD. Using miRNA microarray of aorta specimens from 12 TAD and 12 controls, we identified miR-134-5p, which was significantly downregulated in TAD tissues. With qPCR detection, we found that miR-134-5p was also evidently decreased in human AoSMCs. Ectopic expression of miR-134-5p obviously promoted VSMC differentiation and expression of contractile markers, such as ?-SMA, SM22?, and MYH11. miR-134-5p potently inhibited PDGF-BB-induced VSMC phenotypic switch and migration. We further identified STAT5B and ITGB1 as downstream targets of miR-134-5p in human VSMCs and proved them to be mediators in VSMC phenotypic switch and progression of TAD. Finally, Ad-miR-134-5p obviously suppressed the aorta dilatation and vascular media degeneration by 39% in TAD mice after vascular injury induced by Ang II. Our findings revealed that miR-134-5p was a novel regulator in vascular remodeling and pathological progress of TAD via targeting STAT5B/ITGB1 expression. Targeting miR-134-5p or its downstream molecules in VSMCs might develop new avenues in clinical treatment of TAD.

SUBMITTER: Wang Y

PROVIDER: S-EPMC6446055 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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MicroRNA-134-5p Regulates Media Degeneration through Inhibiting VSMC Phenotypic Switch and Migration in Thoracic Aortic Dissection.

Wang Ying Y Dong Chang-Qing CQ Peng Guang-Yin GY Huang Hao-Yue HY Yu Yun-Sheng YS Ji Zhen-Chun ZC Shen Zhen-Ya ZY

Molecular therapy. Nucleic acids 20190228

Abnormal phenotypic switch, migration, and proliferation of vascular smooth muscle cells (VSMCs) are hallmarks for pathogenesis of thoracic aortic dissection (TAD). In the current study, we identified miR-134-5p as a critical regulator controlling human VSMC phenotypic switch and migration to investigate whether miR-134-5p affects human VSMC functions and development of TAD. Using miRNA microarray of aorta specimens from 12 TAD and 12 controls, we identified miR-134-5p, which was significantly d ...[more]

PMID: 30951965

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Project description:BackgroundThe Food and Drug Administration has approved devices for endovascular management of thoracic endovascular aortic aneurysm repair (TEVAR); however, limited data exist describing the outcomes of TEVAR for aneurysms attributable to chronic type B aortic dissection (cTBAD). This study was undertaken to determine the results of endovascular treatment of cTBAD with aneurysmal degeneration.MethodsA retrospective analysis of all patients treated for cTBAD with aneurysmal degeneration at the University of Florida from 2004 to 2011 was performed. Computed tomograms with centerline reconstruction were analyzed to determine change in aortic diameter, relative proportions of aortic treatment lengths, and false lumen perfusion status. Reintervention and mortality were estimated using life-tables. Cox regression analysis was completed to predict mortality.ResultsEighty patients underwent TEVAR for aneurysm due to cTBAD (mean age [± standard deviation], 60 ± 13 years [male, 87.5%; n = 70]; median follow-up, 26 [range, 1-74] months). Median time from diagnosis of TBAD to TEVAR was 16 (range, 1-72) months. Prior aortic root/arch replacement had been performed in 29% (n = 23) at a median interval of 28.5 (range, 0.5-312) months. Mean preoperative aneurysm diameter was 62.0 ± 9.9 mm. In 75% (n = 60) of cases, coverage was proximal to zone 3, and 24% (n = 19) underwent carotid-subclavian bypass or other arch debranching procedure. Spinal drains were used in 78% (pre-op 71%, n = 57; post-op 6%, n = 5). Length of stay was 6.5 ± 4.7 days with a composite morbidity of 26% and in-hospital mortality of 2.5% (n = 2). Overall neurologic event rate was 17% (spinal cord ischemia 10% [n = 8], with a permanent deficit observed in 6.2% [n = 5]; stroke 7.5%). Aneurysm diameter reduced or stabilized in 65%. The false lumen thrombosed completely within the thoracic aorta in 52%, and reintervention within the treated aortic segment was required in 16% (n = 13).One- and 3-year freedom from reintervention (with 95% confidence interval [CI]) was 80% (range, 68%-88%) and 70% (range, 57%-80%), respectively. Survival at 1 and 5 years was 89% (range, 80%-94%) and 70% (range, 55%-81%) and was not significantly different among patients requiring reintervention or experiencing favorable aortic remodeling. Multivariable analysis identified coronary artery disease (hazard ratio [HR], 6.4; 95% CI, 2.3-17.7; P < .005), prior infrarenal aortic surgery (HR, 8.6; 95% CI, 2.3-31.7; P = .001), and congestive heart failure (HR, 11.9; 95% CI, 1.9-73.8; P = .008) as independent risk factors for mortality. Hyperlipidemia was found to be protective (HR, 0.2; 95% CI, 0.05-0.6; P = .004). No significant difference in predictors of mortality were found between patients who underwent reintervention vs those who did not (P = .2).ConclusionsTEVAR for cTBAD with aneurysmal degeneration can be performed safely but spinal cord ischemia rates may be higher than previously reported. Liberal use of procedural adjuncts to reduce this complication, such as spinal drainage, is recommended. Reintervention is common, but long-term survival does not appear to be impacted by remediation.

Dataset Information

MicroRNA-134-5p Regulates Media Degeneration through Inhibiting VSMC Phenotypic Switch and Migration in Thoracic Aortic Dissection.

Publications

MicroRNA-134-5p Regulates Media Degeneration through Inhibiting VSMC Phenotypic Switch and Migration in Thoracic Aortic Dissection.

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