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Deletion of calponin 2 in macrophages alters cytoskeleton-based functions and attenuates the development of atherosclerosis.
- Source :
-
Journal of molecular and cellular cardiology [J Mol Cell Cardiol] 2016 Oct; Vol. 99, pp. 87-99. Date of Electronic Publication: 2016 Aug 26. - Publication Year :
- 2016
-
Abstract
- Arterial atherosclerosis is an inflammatory disease. Macrophages play a major role in the pathogenesis and progression of atherosclerotic lesions. Modulation of macrophage function is a therapeutic target for the treatment of atherosclerosis. Calponin is an actin-filament-associated regulatory protein that inhibits the activity of myosin-ATPase and dynamics of the actin cytoskeleton. Encoded by the gene Cnn2, calponin isoform 2 is expressed at significant levels in macrophages. Deletion of calponin 2 increases macrophage migration and phagocytosis. In the present study, we investigated the effect of deletion of calponin 2 in macrophages on the pathogenesis and development of atherosclerosis. The results showed that macrophages isolated from Cnn2 knockout mice ingested a similar level of acetylated low-density lipoprotein (LDL) to that of wild type (WT) macrophages but the resulting foam cells had significantly less hindered velocity of migration. Systemic or myeloid cell-specific Cnn2 knockouts effectively attenuated the development of arterial atherosclerosis lesions with less macrophage infiltration in apolipoprotein E knockout mice. Consistently, calponin 2-null macrophages produced less pro-inflammatory cytokines than that of WT macrophages, and the up-regulation of pro-inflammatory cytokines in foam cells was also attenuated by the deletion of calponin 2. Calponin 2-null macrophages and foam cells have significantly weakened cell adhesion, indicating a role of cytoskeleton regulation in macrophage functions and inflammatory responses, and a novel therapeutic target for the treatment of arterial atherosclerosis.<br /> (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Subjects :
- Actin Cytoskeleton metabolism
Animals
Apolipoproteins E deficiency
Atherosclerosis pathology
Cell Adhesion
Cytokines metabolism
Disease Models, Animal
Female
Foam Cells metabolism
Inflammation Mediators
Lipid Metabolism
Male
Mice
Mice, Knockout
Phagocytosis
Plaque, Atherosclerotic pathology
Protein Transport
Calponins
Atherosclerosis genetics
Atherosclerosis metabolism
Calcium-Binding Proteins deficiency
Cytoskeleton metabolism
Macrophages metabolism
Microfilament Proteins deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 1095-8584
- Volume :
- 99
- Database :
- MEDLINE
- Journal :
- Journal of molecular and cellular cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 27575021
- Full Text :
- https://doi.org/10.1016/j.yjmcc.2016.08.019