2026-06-14T03:33:49Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/65772024-09-27T08:09:44Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc del Monte, Alberto author Arroyo, Ana B author Andres-Manzano, Maria J. author Garcia-Barbera, Nuria author Caleprico, Maria S. author Vicente, Vicente author Roldan, Vanessa author Gonzalez-Conejero, Rocio author Martinez, Constantino author Andres, Vicente author 2018 Background Atherosclerosis involves activation of the IRAK1/TRAF6/NF-kappa B inflammatory cascade, which is negatively regulated by miR146a. Previous studies showed that the TT genotype of rs2431697, located near the miR-146a gene, drives lower miR-146a transcription and predicts adverse cardiovascular events in anticoagulated atrial fibrillation patients. Moreover, systemic miR-146a administration protects mice from atherosclerosis. Here we evaluated the ability of miR-146a expression in the hematopoietic component to regulate atherosclerosis in low-density lipoprotein receptor-null mice (LdIr(-/-)). Methods and results Lethally-irradiated LdIr(-/-)mice transplanted with bone marrow from wild-type or miR-146a-null mice were fed an atherogenic diet for 8 and 20 weeks. Irak1, Traf6 and MIR146A expression were quantified in thoracic aorta by qRT-PCR and Western blot. Aortic plaque size and composition were characterized by Oil-Red staining and immunohistochemistry and leukocyte recruitment by intravital microscopy. Blood cell counts were similar in fat-fed Ldir(-/-)mice with or without hematopoietic miR-146a expression. However, plasma cholesterol decreased in fat-fed Ldir(-/-)mice transplanted with bone marrow deficient for miR-146a. Finally, aortic atherosclerosis burden and recruitment of leukocytes into the vessel wall were undistinguishable between the two groups, despite higher levels of Irak1 and Traf6 mRNA and protein in the aorta of fat-fed mice lacking hematopoietic miR-146a expression. Conclusions miR-146a deficiency exclusively in hematopoietic cells modulates cholesterol levels in plasma and the expression of its targets in the artery wall of fat-fed LdIr(-/-)mice, but does not 16 accelerate atherosclerosis. Atheroprotection upon systemic miR-146a administration may therefore be caused by specific effects on vascular cells. PLoS One. 2018; 13(6):e0198932 10.1371/journal.pone.0198932 1932-6203 PLoS ONE 29902229 http://hdl.handle.net/20.500.12105/6577 SYSTEMIC-LUPUS-ERYTHEMATOSUS MICRORNAS MICE MACROPHAGES INFLAMMATION INHIBITION ACTIVATION EXPRESSION PROTECTS BIOLOGY miR-146a deficiency in hematopoietic cells is not involved in the development of atherosclerosis