Chronic miR-29 antagonism promotes favorable plaque remodeling in atherosclerotic mice.
Victoria UlrichNoemi RotllanElisa AraldiAmelia LucianoPhilipp SkroblinMélanie AbonnencPaola PerrottaXiaoke YinAshley BauerKristen L LesliePei ZhangBinod AryalRusty L MontgomeryThomas ThumKathleen MartinYajaira SuarezManuel MayrCarlos Fernandez-HernandoWilliam C SessaPublished in: EMBO molecular medicine (2016)
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.
Keyphrases
- cell proliferation
- extracellular matrix
- long non coding rna
- long noncoding rna
- coronary artery disease
- acute myocardial infarction
- mouse model
- poor prognosis
- heart failure
- dna methylation
- type diabetes
- gene expression
- genome wide
- machine learning
- skeletal muscle
- atrial fibrillation
- signaling pathway
- transcription factor
- metabolic syndrome
- optical coherence tomography
- drug induced
- deep learning