title: miR-24 limits aortic vascular inflammation and murine abdominal aneurysm development.
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.
authors.affiliation: 1] Division of Cardiovascular Medicine, Stanford University, Falk CVRB, 300 Pasteur Drive, Stanford, California 94305, USA [2] Center for Molecular Medicine L8:03, Department of Medicine, Karolinska Institute and University Hospital, Stockholm 17176, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Maegdefessel
authors.affiliation: 1] Division of Cardiovascular Medicine, Stanford University, Falk CVRB, 300 Pasteur Drive, Stanford, California 94305, USA [2] VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304, USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Spin
authors.affiliation: Division of Cardiovascular Medicine, Stanford University, Falk CVRB, 300 Pasteur Drive, Stanford, California 94305, USA.
authors.forename: Uwe
authors.initials: U
authors.lastname: Raaz
authors.affiliation: Center for Molecular Medicine L8:03, Department of Medicine, Karolinska Institute and University Hospital, Stockholm 17176, Sweden.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Eken
authors.affiliation: Division of Cardiovascular Medicine, Stanford University, Falk CVRB, 300 Pasteur Drive, Stanford, California 94305, USA.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Toh
authors.affiliation: Center of Medical Innovation and Translational Research, Department of Clinical Gene Therapy, Osaka University, 2-2 Yamada-oka, Osaka 565-0871, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Azuma
authors.affiliation: Division of Cardiovascular Medicine, Stanford University, Falk CVRB, 300 Pasteur Drive, Stanford, California 94305, USA.
authors.forename: Matti
authors.initials: M
authors.lastname: Adam
authors.forename: Futoshi
authors.initials: F
authors.lastname: Nakagami
authors.affiliation: Division of Cardiovascular Medicine, Stanford University, Falk CVRB, 300 Pasteur Drive, Stanford, California 94305, USA.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Nagakami
authors.affiliation: Division of Cardiovascular Medicine, Stanford University, Falk CVRB, 300 Pasteur Drive, Stanford, California 94305, USA.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Heymann
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Chernogubova
authors.affiliation: Center for Molecular Medicine L8:03, Department of Medicine, Karolinska Institute and University Hospital, Stockholm 17176, Sweden.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Chernugobova
authors.affiliation: Center for Molecular Medicine L8:03, Department of Medicine, Karolinska Institute and University Hospital, Stockholm 17176, Sweden.
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
authors.affiliation: Center for Molecular Medicine L8:03, Department of Molecular Medicine and Surgery, Karolinska Institute and University Hospital, Stockholm 17176, Sweden.
authors.forename: Joy
authors.initials: J
authors.lastname: Roy
authors.affiliation: Center for Molecular Medicine L8:03, Department of Molecular Medicine and Surgery, Karolinska Institute and University Hospital, Stockholm 17176, Sweden.
authors.forename: Rebecka
authors.initials: R
authors.lastname: Hultgren
authors.affiliation: Center for Molecular Medicine L8:03, Department of Molecular Medicine and Surgery, Karolinska Institute and University Hospital, Stockholm 17176, Sweden.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Caidahl
authors.affiliation: Transplant and Stem Cell Immunology Laboratory, University Heart Center Hamburg, Martinistraße 52, Hamburg 20246, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Schrepfer
authors.affiliation: Center for Molecular Medicine L8:03, Department of Medicine, Karolinska Institute and University Hospital, Stockholm 17176, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
authors.affiliation: Center for Molecular Medicine L8:03, Department of Medicine, Karolinska Institute and University Hospital, Stockholm 17176, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
authors.affiliation: Division of Cardiovascular Medicine, Stanford University, Falk CVRB, 300 Pasteur Drive, Stanford, California 94305, USA.
authors.forename: Michael V
authors.initials: MV
authors.lastname: McConnell
authors.affiliation: Division of Vascular Surgery, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Dalman
authors.affiliation: 1] Division of Cardiovascular Medicine, Stanford University, Falk CVRB, 300 Pasteur Drive, Stanford, California 94305, USA [2] VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304, USA.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Tsao
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D000071451:Chitinase-3-Like Protein 1; D004195:Disease Models, Animal; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C509289:Chil1 protein, mouse; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D035683:MicroRNAs; C529080:Mirn24 microRNA, mouse