Abstract

Background: Intermittent fasting and ketogenic diet may improve cardiovascular health. We studied the impact of ketogenic dietary intervention on experimental abdominal aortic aneurysms (AAAs). Methods: AAAs were induced in male mice via topical abluminal porcine pancreatic elastase (PPE) application at laparotomy in C57BL/6J, and 28 day administration of exogenous angiotensin (Ang) II in apolipoprotein E deficient strains, respectively. As feeding regimens, mice were fed standard or ketogenic diets 3 days prior to or 3 days following, AAA induction. Influence on AAA development was assessed by serial transabdominal ultrasonography and histopathologic analysis at sacrifice. Results: Ketogenic diet promotes cardiovascular health in part by increasing ketone body production. The Figure summarizes the influence of ketogenic diet on experimental AAAs in two distinct models. Following PPE application, subsequent aortic diameter enlargement was significantly reduced in mice receiving ketogenic vs. standard diets at 7 and 14 days regardless of specific feeding regimen. On histologic analysis, ketogenic diet feeding resulted in improved aortic medial elastin and smooth muscle cell retention, reduced mural macrophage, CD4 + and CD8 + T and B cell infiltration, and attenuated mural angiogenesis. In the Ang II infusion model, ketogenic diet limited Ang II-induced aortic diameter expansion, lowered AAA incidence and reduced AAA severity. Conclusion: Ketogenic dietary intervention suppressed experimental AAA progression in complementary murine modeling systems. Already popular clinically, this dietary modification may prove effective in limiting clinical AAA disease progression as well as other cardiovascular disease endpoints.