Deletion of calponin 2 in macrophages alters cytoskeleton-based functions and attenuates the development of atherosclerosis. (October 2016)

• Record Type: Journal Article
• Authors: Liu, Rong; Jin, J.-P.
• Is Part Of: Journal of molecular and cellular cardiology. Volume 99(2016:Oct.)
• Page Start: 87
• Page End: 99
• Publication Date: 2016-10
• Subjects: Calponin -- Macrophage -- Atherosclerosis -- Cell motility -- Cell adhesion -- ApoE knockout mouse; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2016.08.019
• Languages: English
• ISSNs: 0022-2828

Abstract

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. Graphic abstract: Deletion of calponin 2 in macrophages attenuates the atherosclerotic lesions in Apo E − / − mice. Highlights: Deletion of calponin 2 in macrophages attenuates atherosclerosis in Apo E − / − mice. Deletion of calponin 2 in macrophages facilitates migration and weakens adhesion. Cnn2 − / − macrophages and foam cells produce lower level of inflammatory cytokines. Calponin 2 may be targeted to treat atherosclerosis and other inflammatory diseases.