Deletion of the FHL2 gene attenuates the formation of atherosclerotic lesions after a cholesterol-enriched diet

AimsFHL2, a member of the four and a half LIM domain (FHL) family of proteins, may play an important role in the circulatory system and in particular atherosclerosis.Main methodsTo investigate the role of FHL2 in atherogenesis, FHL2-null and wild-type control male mice were fed either a normal chow (NC) or a cholesterol-enriched diet (CED).Key findingsAt 3 months post CED, aortic atherosclerotic plaques were observed in both control and FHL2-null mice. Lesions in control mice increased dramatically by 6 months of CED. In contrast, lesion size did not increase during this time in CED-fed FHL2-null mice. Relative to control mice on a normal chow of diet (NCD), control mice on a CED exhibited lower circulating nitric oxide (NO) levels, and decreased expression of connexin37 (Cx37) and Cx40 in aortic endothelium. In contrast, FHL2-null mice on a CED maintained similar levels of circulating NO as FHL2-null mice fed a NCD. Cxs levels in aortic endothelium of FHL2-null mutants on a NCD were lower relative to control mice on a NCD, and did not decrease with CED.SignificanceOur data demonstrate a role for FHL2 in atherogenesis, the regulation of circular NO release, and expression of gap junctions within aortic endothelium.