title: Chronic miR-29 antagonism promotes favorable plaque remodeling in atherosclerotic mice.
abstract: Abnormal remodeling of atherosclerotic plaques can lead to rupture, acute myocardial infarction, and death. Enhancement of plaque extracellular matrix (ECM) may improve plaque morphology and stabilize lesions. Here, we demonstrate that chronic administration of LNA-miR-29 into an atherosclerotic mouse model improves indices of plaque morphology. This occurs due to upregulation of miR-29 target genes of the ECM (col1A and col3A) resulting in reduced lesion size, enhanced fibrous cap thickness, and reduced necrotic zones. Sustained LNA-miR-29 treatment did not affect circulating lipids, blood chemistry, or ECM of solid organs including liver, lung, kidney, spleen, or heart. Collectively, these data support the idea that antagonizing miR-29 may promote beneficial plaque remodeling as an independent approach to stabilize vulnerable atherosclerotic lesions.
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA Department of Pharmacology, School of Medicine Yale University, New Haven, CT, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Ulrich
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA Integrative Cell Signaling and Neurobiology of Metabolism Program, Section of Comparative Medicine and Department of Pathology, School of Medicine Yale University, New Haven, CT, USA.
authors.forename: Noemi
authors.initials: N
authors.lastname: Rotllan
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA Integrative Cell Signaling and Neurobiology of Metabolism Program, Section of Comparative Medicine and Department of Pathology, School of Medicine Yale University, New Haven, CT, USA.
authors.forename: Elisa
authors.initials: E
authors.lastname: Araldi
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA Department of Pharmacology, School of Medicine Yale University, New Haven, CT, USA.
authors.forename: Amelia
authors.initials: A
authors.lastname: Luciano
authors.affiliation: King's British Heart Foundation Centre, King's College London, London, UK.
authors.forename: Philipp
authors.initials: P
authors.lastname: Skroblin
authors.affiliation: King's British Heart Foundation Centre, King's College London, London, UK.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Abonnenc
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA Department of Pharmacology, School of Medicine Yale University, New Haven, CT, USA.
authors.forename: Paola
authors.initials: P
authors.lastname: Perrotta
authors.affiliation: King's British Heart Foundation Centre, King's College London, London, UK.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Yin
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA Department of Cardiology, School of Medicine Yale University, New Haven, CT, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Bauer
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA Department of Cardiology, School of Medicine Yale University, New Haven, CT, USA.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Leslie
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA Department of Pharmacology, School of Medicine Yale University, New Haven, CT, USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA Integrative Cell Signaling and Neurobiology of Metabolism Program, Section of Comparative Medicine and Department of Pathology, School of Medicine Yale University, New Haven, CT, USA.
authors.forename: Binod
authors.initials: B
authors.lastname: Aryal
authors.affiliation: miRagen Therapeutics, Boulder, CO, USA.
authors.forename: Rusty L
authors.initials: RL
authors.lastname: Montgomery
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Thum
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA Department of Cardiology, School of Medicine Yale University, New Haven, CT, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Martin
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA Integrative Cell Signaling and Neurobiology of Metabolism Program, Section of Comparative Medicine and Department of Pathology, School of Medicine Yale University, New Haven, CT, USA.
authors.forename: Yajaira
authors.initials: Y
authors.lastname: Suarez
authors.affiliation: King's British Heart Foundation Centre, King's College London, London, UK.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mayr
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA Integrative Cell Signaling and Neurobiology of Metabolism Program, Section of Comparative Medicine and Department of Pathology, School of Medicine Yale University, New Haven, CT, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernandez-Hernando
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA Department of Pharmacology, School of Medicine Yale University, New Haven, CT, USA william.sessa@yale.edu.
authors.forename: William C
authors.identifier: 0000-0001-5759-1938
authors.initials: WC
authors.lastname: Sessa
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000473:pathology*; D024042:Collagen Type I / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III / Q000378:metabolism; D004195:Disease Models, Animal; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors*
chemical_list: C000609875:COL3A1 protein, mouse; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs
keywords: LNA; atherosclerosis; miR‐29; plaque; stability