miR-24 limits aortic vascular inflammation and murine abdominal aneurysm development

Lars Maegdefessel, Joshua M. Spin, Uwe Raaz, Suzanne M. Eken, Ryuji Toh, Junya Azuma, Matti Adam, Futoshi Nagakami, Helen M. Heymann, Ekaterina Chernugobova, Hong Jin, Joy Roy, Rebecka Hultgren, Kenneth Caidahl, Sonja Schrepfer, Anders Hamsten, Per Eriksson, Michael V. McConnell, Ronald L. Dalman and Philip S. Tsao ()
Additional contact information
Lars Maegdefessel: Stanford University, Falk CVRB, 300 Pasteur Drive
Joshua M. Spin: Stanford University, Falk CVRB, 300 Pasteur Drive
Uwe Raaz: Stanford University, Falk CVRB, 300 Pasteur Drive
Suzanne M. Eken: Center for Molecular Medicine L8:03, Karolinska Institute and University Hospital
Ryuji Toh: Stanford University, Falk CVRB, 300 Pasteur Drive
Junya Azuma: Center of Medical Innovation and Translational Research, Osaka University, 2-2 Yamada-oka
Matti Adam: Stanford University, Falk CVRB, 300 Pasteur Drive
Futoshi Nagakami: Stanford University, Falk CVRB, 300 Pasteur Drive
Helen M. Heymann: Stanford University, Falk CVRB, 300 Pasteur Drive
Ekaterina Chernugobova: Center for Molecular Medicine L8:03, Karolinska Institute and University Hospital
Hong Jin: Center for Molecular Medicine L8:03, Karolinska Institute and University Hospital
Joy Roy: Center for Molecular Medicine L8:03, Karolinska Institute and University Hospital
Rebecka Hultgren: Center for Molecular Medicine L8:03, Karolinska Institute and University Hospital
Kenneth Caidahl: Center for Molecular Medicine L8:03, Karolinska Institute and University Hospital
Sonja Schrepfer: Transplant and Stem Cell Immunology Laboratory, University Heart Center Hamburg, Martinistraße 52
Anders Hamsten: Center for Molecular Medicine L8:03, Karolinska Institute and University Hospital
Per Eriksson: Center for Molecular Medicine L8:03, Karolinska Institute and University Hospital
Michael V. McConnell: Stanford University, Falk CVRB, 300 Pasteur Drive
Ronald L. Dalman: Stanford University, 300 Pasteur Drive
Philip S. Tsao: Stanford University, Falk CVRB, 300 Pasteur Drive

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: Abstract Identification and treatment of abdominal aortic aneurysm (AAA) remain among the most prominent challenges in vascular medicine. MicroRNAs (miRNAs) are crucial regulators of cardiovascular pathology and represent intriguing targets to limit AAA expansion. Here we show, by using two established murine models of AAA disease along with human aortic tissue and plasma analysis, that miR-24 is a key regulator of vascular inflammation and AAA pathology. In vivo and in vitro studies reveal chitinase 3-like 1 (Chi3l1) to be a major target and effector under the control of miR-24, regulating cytokine synthesis in macrophages as well as their survival, promoting aortic smooth muscle cell migration and cytokine production, and stimulating adhesion molecule expression in vascular endothelial cells. We further show that modulation of miR-24 alters AAA progression in animal models, and that miR-24 and CHI3L1 represent novel plasma biomarkers of AAA disease progression in humans.

Date: 2014
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DOI: 10.1038/ncomms6214

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