MicroRNAs as a therapeutic target for cardiovascular diseases

Mishra, Paras Kumar; Tyagi, Neetu; Kumar, Munish; Tyagi, Suresh C.

doi:10.1111/j.1582-4934.2009.00744.x

Cited by 133 publications

(131 citation statements)

References 127 publications

(217 reference statements)

Supporting

Mentioning

127

Contrasting

Unclassified

Order By: Relevance

“…Unlike most traditional therapeutic approaches in which drugs have specific cellular targets, the key component of miR modulation lies in regulation of entire functional gene networks (25). However, this is also a potential weakness of the approach, as unintended off-target effects may occur.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development

Maegdefessel

Azuma²,

Toh³

et al. 2012

J. Clin. Invest.

277

267

View full text Add to dashboard Cite

MicroRNAs (miRs) regulate gene expression at the posttranscriptional level and play crucial roles in vascular integrity. As such, they may have a role in modifying abdominal aortic aneurysm (AAA) expansion, the pathophysiological mechanisms of which remain incompletely explored. Here, we investigate the role of miRs in 2 murine models of experimental AAA: the porcine pancreatic elastase (PPE) infusion model in C57BL/6 mice and the AngII infusion model in Apoe -/-mice. AAA development was accompanied by decreased aortic expression of miR-29b, along with increased expression of known miR-29b targets, Col1a1, Col3a1, Col5a1, and Eln, in both models. In vivo administration of locked nucleic acid anti-miR-29b greatly increased collagen expression, leading to an early fibrotic response in the abdominal aortic wall and resulting in a significant reduction in AAA progression over time in both models. In contrast, overexpression of miR-29b using a lentiviral vector led to augmented AAA expansion and significant increase of aortic rupture rate. Cell culture studies identified aortic fibroblasts as the likely vascular cell type mediating the profibrotic effects of miR-29b modulation. A similar pattern of reduced miR-29b expression and increased target gene expression was observed in human AAA tissue samples compared with that in organ donor controls. These data suggest that therapeutic manipulation of miR29b and its target genes holds promise for limiting AAA disease progression and protecting from rupture.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development

Maegdefessel

Azuma²,

Toh³

et al. 2012

J. Clin. Invest.

277

267

View full text Add to dashboard Cite

show abstract

“…MicroRNAs are small (ϳ22 nt), noncoding RNAs that regulate mRNA and protein expression through mRNA degradation or translational inhibition (10). MiRNAs are rapidly emerging as therapeutic targets for CVD (22,103,108,122,126). H 2 S regulates miRNA expression (70,73,93); however, the interaction between H 2 S and miRNAs in CVD is poorly understood.…”

Section: H 2 S Mitigates Pathological Cardiac Remodeling By Inhibitinmentioning

confidence: 99%

Emerging role of hydrogen sulfide-microRNA crosstalk in cardiovascular diseases

Hackfort

Mishra

2016

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Finally, small non-coding RNAs and RNAi have already been introduced as promising novel drugs in preclinical and clinical trials against various diseases (Blenkiron and Miska, 2007;Lopez-Fraga et al, 2009;Mishra et al, 2009b;Nakasa et al, 2009;Takeshita et al, 2009;Zhang, 2009). The power of small ncRNAs and their derivatives as putative therapeutic molecules together with the still scarce functional knowledge about non-coding RNAs in regard to aging gives all reason to expect many surprises for basic and biomedical aging research in regard to nonconding RNAs.…”

Section: Discussionmentioning

confidence: 99%