Nkx2‐5 Is Expressed in Atherosclerotic Plaques and Attenuates Development of Atherosclerosis in Apolipoprotein E–Deficient Mice

BackgroundNK2 homeobox 5 (Nkx2‐5) is a cardiac homeobox transcription factor that is expressed in a broad range of cardiac sublineages. Embryos lacking Nkx2‐5 are nonviable attributed to growth retardation and gross abnormalities of the heart. However, the role of Nkx2‐5 in atherosclerosis remains elusive. This study aims to elucidate the specific functions of Nkx2‐5 during atherogenesis and in established atherosclerotic plaques. Methods and ResultsTwo types of atherosclerotic lesions were created in ApoE−/− mice through 2 different dietary manipulations. Mice fed a standard chow diet were sacrificed at 20 weeks old, a time point at which mice developed early‐stage atherosclerotic lesions. The other half of mice were fed a western diet from 6 to 22 weeks old and then sacrificed. These mice demonstrated advanced atherosclerosis. No Nkx2‐5 was detected in normal arteries; however, it was abundantly present in the intima of atherosclerotic lesions and localized in macrophages and smooth muscle cells. Adenov...