Mast Cell Deficiency Attenuates Atherosclerosis in Apolipoprotein E‐deficient mice

Mast cells (MC) are important cells of the immune system and are recognized as participants in the progression of atherosclerosis. To test MC's role in atherosclerosis in vivo, apolipoprotein E‐deficient (ApoE −/− ) mice were crossed with MC‐deficient Kit W‐sh/W–sh mice to obtain an apoE −/− /Kit W‐sh/W–sh double knockout mouse model. To induce atherosclerosis, ApoE −/− , Kit W‐sh/W–sh , and ApoE −/− /Kit W‐sh/W–sh mice were maintained on a Western Diet for 80 to 90 days. The mice were then killed, blood was collected, and the aorta was perfused in situ first with PBS and then with buffered 10% formalin and processed for cross‐sectional analyses of plaque size in the arch or thoracic region, or processed for en face analyses for plaques after Sudan III staining. H and E slides were digitally scanned on ScanScope XT system and images were evaluated for plaques thickness. Plaque thickness in aortic cross sections were significantly different between ApoE −/− (203μm, n=6) and ApoE −/− /Kit W‐sh/W–sh mouse (120μm, n=7) with no lesions in the Kit W‐sh/W–sh mouse. The en face analyses of aortas also showed reduced atherosclerotic area in ApoE −/− /Kit W‐sh/W–sh mice with no aortic plaque formation in Kit W‐sh/W–sh mice. MCs with indications of degranulation were seen only in the aortic walls of ApoE −/− mice. In comparison to ApoE −/− mice, the cholesterol levels were 50% lower in apoE −/− /Kit W‐sh/W–sh mice while no appreciable difference in triglycerides were noted. Results demonstrate the involvement of MC in the progression of atherosclerosis. The mechanisms by which MC enhance atherosclerotic plaque development remain to be elucidated. (Supported by NIH R01‐HL070101 and Carey Arthritis Fund)