Progressive Aortic Dilation Is Regulated by miR-17–Associated miRNAs

Wu, Jie; Song, Hui‐Fang; Li, Shuhong; Guo, Jian; Tsang, Katherine; Tumiati, Laura C.; Butany, Jagdish; Yau, Terrence M.; Ouzounian, Maral; Fu, Songbin; David, Tirone E.; Weisel, Richard D.; Li, Ren‐Ke

doi:10.1016/j.jacc.2016.04.027

Cited by 52 publications

(55 citation statements)

References 25 publications

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“…Using porcine valvular interstitial cells and human valve leaflets, Yanagawa et al [29] determined that the down-regulation of miR-141 in stenotic bicuspid leaflets regulates BMP-2-mediated valve calcification. Wu et al [30] performed a paired comparison of the miRNA expression between severely dilated and normal-appearing, less-dilated aortic samples, associating the differential regulation of the miR-17 gene cluster with the predisposition to dilation through the dysregulation of the matrix metalloproteinases-tissue inhibitors of matrix metalloproteinases (TIMP-MMP) pathway. However, although the determination of the miRNA expression profile in tissue samples provides valuable information regarding the pathophysiological mechanisms underlying diseases, this expression signature often cannot be extrapolated to the bloodstream.…”

Section: Discussionmentioning

confidence: 99%

Specific circulating microRNA signature of bicuspid aortic valve disease

et al. 2017

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BackgroundWe aimed to determine the circulating miRNA expression profile associated with BAV and aortic dilation to provide diagnostic and prognostic biomarkers for BAV and/or aortic dilation.Methods and resultsWe applied a miRNome-wide microarray approach using plasma samples (n = 24) from healthy tricuspid aortic valve individuals, BAV patients and BAV patients with aortic dilation to compare and identify the specific miRNAs associated with BAV and aortic dilation. In a second stage, the expression patterns of the miRNA candidates were validated by RT-qPCR in an independent cohort (n = 43). The miRNA microarray data and RT-qPCR analyses revealed that the expression levels of circulating miR-122, miR-130a and miR-486 are significantly influenced by the morphology of the aortic valve (bicuspid/tricuspid) and could be functionally involved in the regulation of TGF-β1 signalling. Furthermore, the expression pattern of miR-718 in the plasma was strongly influenced by dilation of the ascending aorta. miR-718 expression was inversely correlated with the aortic diameter (R = −0.63, p = 3.1 × 10−5) and was an independent predictor of aortic dilation (β = −0.41, p = 0.022). The genes targeted by miR-718 are involved in the regulation of vascular remodelling.ConclusionsWe propose that miR-122, miR-130a, miR-486 and miR-718 are new molecular features associated with BAV and aortic dilation principally by the activation of TGF-β1 pathway and vascular remodelling mediated by VEGF signalling pathways.

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Section: Discussionmentioning

confidence: 99%

Specific circulating microRNA signature of bicuspid aortic valve disease

et al. 2017

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“…Recently, a new cluster of miRNAs (miR-17-associated miRNAs) was identified in progressive aortic dilation (Wu et al, 2016). Patients with a bicuspid aortic valve (BAV) are at increased risk for progressive aortic dilation associated with ECM degradation, relating to the increased activity of MMPs.…”

Section: Mirnas In Taasmentioning

confidence: 99%

Non-coding RNA Contribution to Thoracic and Abdominal Aortic Aneurysm Disease Development and Progression

Maegdefessel

2017

Front. Physiol.

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Multiple research groups have started to uncover the complex genetic and epigenetic machinery necessary to maintain cardiovascular homeostasis. In particular, the key contribution of non-coding RNAs (ncRNAs) in regulating gene expression has recently received great attention. Aneurysms in varying locations of the aorta are defined as permanent dilations, predisposing to the fatal consequence of rupture. The characteristic pathology of an aneurysm is characterized by progressive vessel wall dilation, promoted by dying vascular smooth muscle cells and limited proliferation, as well as impaired synthesis and degradation of extracellular matrix components, which at least partially is the result of transmural inflammation and its disruptive effect on vessel wall homeostasis. Currently no conservative pharmacological approach exists that could slow down aneurysm progression and protect from the risk of acute rupture. In the recent past, several non-coding RNAs (mainly microRNAs) have been discovered as being involved in aneurysm progression throughout varying locations of the aorta. Exploring ncRNAs as key regulators and potential therapeutic targets by using antisense oligonucleotide strategies could open up promising opportunities for patients in the near future. Purpose of this current review is to summarize current findings and novel concepts of perspectivly utilizing ncRNAs for future therapeutic and biomarker applications.

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“…6,7 However, recent papers continue to identify aspects of BAV-associated aortopathies, including increased levels of matrix metalloproteinases 2 and 9 with concomitant decline in their inhibitors and dysregulation of cardioprotective signaling molecules that thereby establish a milieu promoting pathology within the aortic wall. [8][9][10] Such cellular changes inevitably lead to pathological changes in overall aortic physiology and altered biomechanics that are reflected in studies showing reduced aortic elasticity and increased stiffness in BAV and associated with poor cardiovascular outcomes. [11][12][13] How to directly assess such physiological and cellular changes through imaging remains in development.…”

Section: See Article By Masri Et Almentioning

confidence: 99%