Our mission is to become a worldwide reference for education in the field for all professionals involved in the process to disseminate knowledge & skills of Acute Cardiovascular Care.
Our mission is to promote excellence in clinical diagnosis, research, technical development, and education in cardiovascular imaging in Europe.
Our mission is to promote excellence in research, practice, education and policy in cardiovascular health, primary and secondary prevention.
Our mission is to reduce the burden of cardiovascular disease through percutaneous cardiovascular interventions.
Improving the quality of life and reducing sudden cardiac death by limiting the impact of heart rhythm disturbances.
Our mission is to improve quality of life and longevity, through better prevention, diagnosis and treatment of heart failure, including the establishment of networks for its management, education and research.
The ESC Working Groups' goal is to stimulate and disseminate scientific knowledge in different fields of cardiology.
The ESC Councils' goal is to share knowledge among medical professionals practising in specific cardiology domains.
OUR MISSION: TO REDUCE THE BURDEN OF CARDIOVASCULAR DISEASE
Mr Lars Maegdefessel
Lars MaegdefesselAccess to the congress content with ESC Congress 365
List of Authors: Lars Maegdefessel (1,2), Uwe Raaz (1), Joshua M. Spin (1), Per Eriksson (2), Anders Hamsten (2), Philip S. Tsao (1)
Identification and treatment of abdominal aortic aneurysm (AAA) remain among the most prominent challenges in vascular medicine. MicroRNAs (miRs) are crucial regulators of cardiovascular pathology, and represent intriguing novel targets for the inhibition of AAA expansion. Using microarray as well as qRT-PCR techniques we were able to identify miR-24 as a key modulator of inflammation and fibrosis in developing AAA in two established murine models: porcine-pancreatic-elastase in male 10 weeks old C57/Bl6 mice, and angiotensin II-infusion in male 10 weeks old apoE-/- mice. In both models, miR-24 downregulation was accompanied by increased expression of YKL-40 (chitinase 3 like-1 = Chi3l1), a newly identified regulator of inflammation and tissue remodeling in vascular diseases and rheumatoid arthritis, and a putative target of miR-24. Lentiviral overexpression of miR-24 inhibited YKL-40 induction within the aortic wall, significantly reduced inflammatory activity and macrophage infiltration, and stimulated tissue remodeling. This was associated with a dramatic decrease in AAA expansion in both mouse models. In contrast, systemic injection of a lentiviral vector carrying an antagomiR targeting miR-24 further increased YKL-40 expression, augmented the inflammatory response, and attenuated fibrosis, with concomitant acceleration of AAA progression. Importantly, similar findings of miR-24 and YKL-40 expression and regulation were observed in human aortic tissue samples from patients undergoing surgical AAA repair as compared to non-dilated control aortas. Furthermore, YKL-40 plasma levels were substantially increased in patients with AAA compared to control patients with a significant further increase in patients with large AAA compared to smaller AAA. In vitro studies in human aortic smooth muscle cells and macrophages identified NF-κB signaling as a key regulator of miR-24 expression. Counteracting miR-24 downregulation shows great potential as a novel and powerful therapeutic option to limit AAA disease progression by targeting inflammatory and tissue remodeling processes in the aortic wall. Furthermore, YKL-40 appears as an intriguing novel biomarker to identify human AAA disease severity.
1:Stanford University, Stanford, CA (USA), Division of Cardiovascular Medicine2:Karolinska Institute, Stockholm (Sweden), Department of Medicine, Atherosclerosis Research Unit
Basic and Translational Science Hot Line
© 2017 European Society of Cardiology. All rights reserved