Absence of Four-and-a-Half LIM Domain Protein 2 Decreases Atherosclerosis in ApoE−/− Mice. Issue 5 (May 2015)

• Record Type: Journal Article
• Authors: Ebrahimian, Talin; Simon, David; Lemarié, Catherine A.; Simeone, Stefania; Heidari, Maryam; Mann, Koren K.; Wassmann, Sven; Lehoux, Stephanie
• Is Part Of: Arteriosclerosis, thrombosis, and vascular biology. Volume 35:Issue 5(2015)
• Publication Date: 2015-05
• Subjects: Arteriosclerosis -- Periodicals; Thrombosis -- Periodicals; Blood-vessels -- Pathophysiology -- Periodicals; Electronic journals; 616.13
• DOI: 10.1161/ATVBAHA.114.305071
• Languages: English
• ISSNs: 1079-5642

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Objective—</title> <p>Four-and-a-half LIM domain protein-2 (FHL2) is expressed in endothelial cells, vascular smooth muscle cells, and leukocytes. It regulates cell survival, migration, and inflammatory response, but its role in atherogenesis is unknown.</p> </sec> <sec> <title>Approach and Results—</title> <p>To investigate the role of FHL2 in atherosclerosis, FHL2-deficient mice were crossed with ApoE-deficient mice, to generate ApoE/FHL2−/− mice. After high-fat diet, ApoE/FHL2−/− mice had significantly smaller atherosclerotic plaques than ApoE−/− mice in the aortic sinus, the brachiocephalic artery, and the aorta. This was associated with enhanced collagen and smooth muscle cell contents and a 2-fold reduction in macrophage content within the plaques of ApoE/FHL-2−/− versus ApoE−/− mice. This could be explained, in part, by the reduction in aortic ICAM-1 (intracellular adhesion molecule) mRNA and VCAM-1 (vascular cell adhesion molecule) protein expression in the plaque. Aortic gene expression of the chemokines CX3CL1 and CCL5 was increased in ApoE/FHL2−/− versus ApoE−/− mice. Peritoneal thioglycollate injection elicited equivalent numbers of monocytes and macrophages in both groups, but a significantly lower number of proinflammatory Ly6C high monocytes were recruited in ApoE/FHL2−/− versus ApoE−/− mice. Furthermore, mRNA levels of CX3CR1 were 2-fold higher in monocytes from ApoE/FHL2−/− versus ApoE−/− mice. Finally, we investigated the potential importance of myeloid cell FHL2 deficiency in atherosclerosis. After being irradiated, ApoE−/− or ApoE/FHL2−/− mice were transplanted with ApoE−/− or ApoE/FHL2−/− bone marrow. After high-fat diet, both chimeric groups developed smaller plaques than ApoE−/− transplanted with ApoE−/− bone marrow.</p> </sec> <sec> <title>Conclusions—</title> <p>These results suggest that FHL2 in both myeloid and vascular cells may play an important role in atherosclerosis by promoting proinflammatory chemokine production, adhesion molecule expression, and proinflammatory monocyte recruitment.</p> </sec> </abstract>