MicroRNAs, fibrotic remodeling, and aortic aneurysms

Abstract

Aortic aneurysms are a common clinical condition that can cause death due to aortic dissection or rupture. The association between aortic aneurysm pathogenesis and altered TGF-b signaling has been the subject of numerous investigations. Recently, a TGF-b-responsive microRNA (miR), miR-29, has been identified to play a role in cellular phenotypic modulation during aortic development and aging. In this issue of JCI, Maegdefessel and colleagues demonstrate that decreasing the levels of miR-29b in the aortic wall can attenuate aortic aneurysm progression in two different mouse models of abdominal aortic aneurysms. This study highlights the relevance of miR-29b in aortic disease but also raises questions about its specific role.

Novel Mechanisms of Abdominal Aortic Aneurysms

“…In AngII-infused ApoE−/− mice, miR-29b manipulation resulted in rather modest changes of aortic diameters [109 XX]. Potential mechanisms of the conflicting findings in these two studies have been discussed in a recent commentary [111]. …”

“…In contrast to the contribution of miR-29b to AAAs, overexpression of miR-21 prevented AAA formation, whereas inhibition of miR-21 augmented AAA formation [112]. Overall, reported studies have recognized the potential importance of microRNAs in the development of AAAs, which may involve classically defined pathways such as extracellular matrix protein degeneration/regeneration and TGF-β signaling [111]. …”

MicroRNA-29b regulation of abdominal aortic aneurysm development

“…AAA pathology is characterized by progressive aortic dilation, which is promoted by an imbalance of vascular smooth muscle cell proliferation and apoptosis, as well as distinct impairment of extracellular matrix synthesis and degradation, which is partly due to transmural inflammation and its disruptive effect on vessel wall homeostasis(Lu, Rateri et al 2012, Milewicz 2012). …”

“…Based on these observations, miR-29 is likely to be a crucial regulator of aortic aneurysm disease by modulating several genes and pathways responsible for ECM composition, dynamics, and disease contributing impairment(Milewicz 2012). In murine AAA experiments from Maegdefessel et al (Maegdefessel, Azuma et al 2012), miR-29b was the only member of the miR-29 family that was significantly down-regulated at three different time points during murine AAA development and progression.…”

Recent Developments in Cardiovascular Genetics and Genomics

“…12,84,[92][93][94][95][96][97] Similarly, a large number of microRNAs are implicated in vascular phenotypes ranging from pulmonary hypertension to aortic aneurysm. 77,79,[98][99][100][101][102][103][104][105][106][107] For example, microRNA-145 was recently shown to be upregulated in the lung tissue of patients with pulmonary hypertension and might be a contributing factor to the pathogenesis of pulmonary hypertension. 108 MicroRNA-10, microRNA-15a, microRNA-16, microRNA-26a, microR-NA-223, and microRNA-663 are involved in angiogenesis and regulate vascular smooth muscle and endothelial cell phenotypes.…”