Antagonism of miR-148a attenuates atherosclerosis progression in APOBTGApobec-/-Ldlr+/- mice : A brief report
Rotllan, Noemi (Institut d'Investigació Biomèdica Sant Pau)
Zhang, X. (Yale University School of Medicine)
Canfrán-Duque, A. (Yale University School of Medicine)
Goedeke, L. (Yale University School of Medicine)
Griñán, Raquel (Institut d'Investigació Biomèdica Sant Pau)
Ramírez, C.M. (IMDEA Research Institute of Food and Health Sciences)
Suárez, Y. (Yale University School of Medicine)
Fernández-Hernando, C. (Yale University School of Medicine)
Universitat Autònoma de Barcelona

Data:	2022
Resum:	miR-148a-3p (miR-148a) is a hepatic and immune-enriched microRNA (miRNA) that regulates macrophage-related lipoprotein metabolism, cholesterol homeostasis, and inflammation. The contribution of miR-148a-3p to the progression of atherosclerosis is unknown. In this study, we determined whether miR-148a silencing mitigated atherogenesis in APOBApobecLdlr mice. APOBApobecLdlr mice were fed a typical Western-style diet for 22 weeks and injected with a nontargeting locked nucleic acid (LNA; LNA control) or miR-148a LNA (LNA 148a) for the last 10 weeks. At the end of the treatment, the mice were sacrificed, and circulating lipids, hepatic gene expression, and atherosclerotic lesions were analyzed. Examination of atherosclerotic lesions revealed a significant reduction in plaque size, with marked remodeling of the lesions toward a more stable phenotype. Mechanistically, miR-148a levels influenced macrophage cholesterol efflux and the inflammatory response. Suppression of miR-148a in murine primary macrophages decreased mRNA levels of proinflammatory M1-like markers (Nos2, Il6, Cox2, and Tnf) and increased the expression of anti-inflammatory genes (Arg1, Retlna, and Mrc1). Therapeutic silencing of miR148a mitigated the progression of atherosclerosis and promoted plaque stability. The antiatherogenic effect of miR-148a antisense therapy is likely mediated by the anti-inflammatory effects observed in macrophages treated with miR-148 LNA and independent of significant changes in circulating low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C).
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Atherosclerosis progression ; Cholesterol Efflux ; M2-like phenotype ; MiR-148a ; Plaque stability ; Therapeutic inhibition
Publicat a:	Biomedicine & pharmacotherapy, Vol. 153 (september 2022) , p. 113419, ISSN 1950-6007

DOI: 10.1016/j.biopha.2022.113419
PMID: 36076541

8 p, 2.9 MB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Recerca Sant Pau
Articles > Articles de recerca
Articles > Articles publicats