miR-24 limits aortic vascular inflammation and murine abdominal aneurysm development
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miR-24 limits aortic vascular inflammation and murine abdominal aneurysm development. / Maegdefessel, Lars; Spin, Joshua M; Raaz, Uwe; Eken, Suzanne M; Toh, Ryuji; Azuma, Junya; Adam, Matti; Nakagami, Futoshi; Nagakami, Futoshi; Heymann, Helen M; Chernogubova, Ekaterina; Chernugobova, Ekaterina; Jin, Hong; Roy, Joy; Hultgren, Rebecka; Caidahl, Kenneth; Schrepfer, Sonja; Hamsten, Anders; Eriksson, Per; McConnell, Michael V; Dalman, Ronald L; Tsao, Philip S.
in: NAT COMMUN, Jahrgang 5, 31.10.2014, S. 5214.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - miR-24 limits aortic vascular inflammation and murine abdominal aneurysm development
AU - Maegdefessel, Lars
AU - Spin, Joshua M
AU - Raaz, Uwe
AU - Eken, Suzanne M
AU - Toh, Ryuji
AU - Azuma, Junya
AU - Adam, Matti
AU - Nakagami, Futoshi
AU - Nagakami, Futoshi
AU - Heymann, Helen M
AU - Chernogubova, Ekaterina
AU - Chernugobova, Ekaterina
AU - Jin, Hong
AU - Roy, Joy
AU - Hultgren, Rebecka
AU - Caidahl, Kenneth
AU - Schrepfer, Sonja
AU - Hamsten, Anders
AU - Eriksson, Per
AU - McConnell, Michael V
AU - Dalman, Ronald L
AU - Tsao, Philip S
PY - 2014/10/31
Y1 - 2014/10/31
N2 - 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.
AB - 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.
KW - Animals
KW - Aorta/metabolism
KW - Aortic Aneurysm, Abdominal/etiology
KW - Biomarkers/blood
KW - Cells, Cultured
KW - Chitinase-3-Like Protein 1
KW - Disease Models, Animal
KW - Disease Progression
KW - Endothelial Cells/metabolism
KW - Glycoproteins/metabolism
KW - Humans
KW - Inflammation/metabolism
KW - Macrophages/metabolism
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - MicroRNAs/metabolism
KW - Myocytes, Smooth Muscle/metabolism
U2 - 10.1038/ncomms6214
DO - 10.1038/ncomms6214
M3 - SCORING: Journal article
C2 - 25358394
VL - 5
SP - 5214
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
ER -