Abstract 9713: Ketosis Decreases Murine Plaque and Aortic Aneurysm Formation

Abstract

Introduction: Atherosclerosis and aortic aneurysm (AA) are associated with leading causes of mortality worldwide. There is no medical therapy for the treatment of AA, and though diet modification is essential for the management of cardiovascular disease. A ketogenic diet has been accepted as an effective complementary treatment for hypertension and dyslipidemia. Hypothesis: We sought to evaluate if a high fat, low carbohydrate diet could attenuate plaque and AA formation in a mouse model. Methods: Apo E -/- mice (N=30) 12 weeks old, underwent Angiotensin II pump administration, with daily provision of β-aminopropionitrile (BAPN) over 28 days. Control mice (StD, N=15) received a standard diet (fat 42%, carbohydrates 42.7%, proteins 15.2%); while mice undergoing ketosis induction (KD, N=15) received a high fat, low carbohydrate diet (fat 90.5%, carbohydrates 0.3%, proteins 9.2%). Ketosis was achieved by a β-hydroxybutyrate (BHB) whole blood level >0.5 mmol/L. After 28 days, aortic diameters were measured by surgical microscopy. Isolated whole aortas were en-faced and stained with oil red O (ORO) to assess the grade of lesion area (plaque area + aneurysm degeneration area / whole aorta’s area) and plaque content (plaque area / whole aorta’s area). Results: KD mice remained in a ketotic state throughout the experiment. Thoracic and infrarenal AAs were identified in 60% and 74% of StD mice, respectively; however, only 13% and 33% of KD mice developed thoracic and infrarenal AAs, respectively. ORO staining (Fig. 1C and G) demonstrated a significantly smaller lesion area in KD mice (p = 0.04), (Fig. 1D). Furthermore, KD plaque content was attenuated in each segment of the aorta yet only significant in the thoracic aorta (p = 0.04), (Fig. 1H). Conclusions: Our results demonstrate that a ketogenic diet can attenuate the development of atherosclerotic plaque and AA degeneration in mice.