Nicotine and miR-24 in abdominal aortic aneurysm

• Applicant: Privatdozent Dr. Matti Adam
• Subject Area: Cardiology, Angiology
• Term: from 2014 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 261320225

Abdominal aortic aneurysm (AAA) is a common, morbid and highly lethal disease. There are currently no non-invasive therapeutic strategies that significantly limit or prevent AAA growth and formation. Therefore, the understanding of the underlying molecular mechanisms of AAA disease and progression are of utmost importance. While advanced age, genetic predilection, and male sex are relevant AAA risk factors, a history of tobacco use is the most important modifiable risk factor. In fact, more than 90 percent of individuals diagnosed with AAA are either current or prior tobacco users, and ongoing smoking is associated with accelerated aneurysm expansion. The applicant's host lab has found that the tobacco-component, nicotine, can accelerate AAA formation in two murine models. Concomitant with this, we have observed down-regulation of microRNA-24 (miR-24). This is of particular interest, as posttranscriptional regulation by microRNAs, e.g. miR-21 and miR-29b, has been shown to be a critical component of AAA formation and growth. Furthermore, several predicted gene targets of miR-24 are enriched in pro-inflammatory pathways. Conclusively, it is hypothesized that nicotine causes down-regulation of aortic miR-24, resulting in elevated expression of genes related to inflammation, and accelerated AAA disease. This would imply an important protective role for miR-24 in vascular inflammation during AAA formation and growth. Enhancing miR-24 expression and activity within the aortic wall in vivo may therefore have therapeutic benefit in AAA.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Philip S. Tsao, Ph.D.