Abstract 19389: Hematopoietic mir-21 Deficiency Promotes Apoptosis and Plaque Necrosis in Advanced Atherosclerotic Lesions
Objective: To address the role of miR-21 during the progression of atherosclerosis.
Introduction: Micro-RNAs (miRNAs) are a class of short non-coding RNAs known to be involved in many different biological processes, including vascular physiology, lipid metabolism and inflammation. Specifically, our group has made important contributions to this field, showing a key role for several miRNAs during the progression of atherosclerosis and lipoprotein metabolism. In the present work, we studied the role of miR-21 in the development of atherosclerosis. miR-21 is the most abundant miRNA in macrophages and its expression has been associated with the resolution of inflammation and the negative regulation of pro-inflammatory responses in macrophages. These observations strongly suggest that macrophage miR-21 expression may influence atherogenesis.
Methods and results: To assess the role of miR-21 in macrophages during the progression of atherosclerosis, 8 week-old Ldlr-/- mice were transplanted with bone marrow from wild-type or miR-21-/- mice and fed a Western diet for 12 weeks. Analysis of atherosclerotic plaques revealed that Ldlr-/- mice transplanted with miR-21-/- bone marrow developed more advanced plaques compared to Ldlr-/- mice transplanted with wild-type bone marrow. Specifically, we observed that mice transplanted with miR-21-/- bone marrow cells developed significantly larger lesions, with more apoptotic cells and more necrotic area, and the lesions exhibited less fibrous cap thickness. Macrophage apoptosis and defective phagocytic clearance of dead cells (efferocytosis) promotes plaque necrosis and inflammation. In our in vitro studies we found that lack of miR-21 enhanced ER stress-induced macrophage apoptosis and impaired the process of efferocytosis.
Conclusions: Taken together, our results demonstrate that miR-21 plays a key role in the progression of atherosclerosis by influencing ER-stress-induced apoptosis and advanced lesion macrophage apoptosis.
Key Words: miR-21, macrophages, atherosclerosis.
Author Disclosures: A. Canfrán-Duque: None. N. Rotllan: None. E. Araldi: None. X. Zhang: None. L. Daimiel: None. C. Fernández-Hernando: None. Y. Suárez: None.
- © 2016 by American Heart Association, Inc.