Research ArticleVascular Disease

MicroRNA-21 Blocks Abdominal Aortic Aneurysm Development and Nicotine-Augmented Expansion

Science Translational Medicine  22 Feb 2012:
Vol. 4, Issue 122, pp. 122ra22
DOI: 10.1126/scitranslmed.3003441

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miR-21, a Red Alert for AAA

Abdominal aortic aneurysms (AAAs) constitute a major public health burden, with few treatment options. In this common condition associated with increased age, male gender, high blood pressure, and especially smoking, the major conduit vessel within the abdomen slowly enlarges and may rupture, often fatally. MicroRNAs are short molecules that can simultaneously regulate translation of multiple genes. One example, microRNA-21 (miR-21), has been shown to control gene expression patterns that influence a variety of cellular processes including maturation, migration, proliferation, and survival. In a new study, Maegdefessel et al. investigated the role of miR-21 in two well-established mouse models of AAA: one in which the aorta is exposed to enzymatic degradation of supporting tissue and another in which mice predisposed to vascular disease spontaneously form AAA in response to the peptide hormone angiotensin II. In both models, miR-21 expression increased within the aortic wall as the AAA developed. miR-21 was also elevated in samples of aorta from patients with AAA compared with healthy controls. Nicotine, the major constituent of tobacco, accelerated AAA growth in both mouse models and caused an even larger increase in miR-21 expression. This appeared to be a protective response because preventing an increase in miR-21 with an inhibitor increased AAA growth and rupture rates in both models. In contrast, exogenous supplementation of miR-21 slowed aneurysm growth and prevented rupture, even in the presence of nicotine. This was partly mediated through miR-21’s suppressive effects on the protein PTEN (phosphatase and tensin homolog). Cell culture studies demonstrated that inflammatory stimuli, known to influence AAA development, increased miR-21 expression. These results suggest that enhanced miR-21 expression is an endogenous response to pathological aortic dilation and may offer a new therapeutic pathway that could be targeted to treat AAA in patients.