Abstract We0019: Time-restricted feeding attenuates experimental abdominal aortic aneurysms

Background: Time-restricted feeding (TRF)/intermittent fasting is associated with improved outcomes for cardiovascular and metabolic disorders and expanded lifespan. It has not been investigated whether TRF influences experimental abdominal aortic aneurysm (AAA). Methods: AAAs were induced in 9-10 weeks old male C57BL/6J mice by painting porcine pancreatic elastase on infrarenal aortic external wall. Mice were daily fasted for 16 hours (5 PM to 9 AM) starting 3 days prior to (preventive) or 4 days following (therapeutic) AAA induction, with mice without fasting serving as the controls. AAA progression was monitored via serial ultrasound measurements of maximal infrarenal aortic diameter. Fourteen days following AAA induction, mice were euthanized, and aortae were harvested for histopathological analysis. Results: TRF significantly inhibited experimental AAA enlargement as compared to non-fasting controls regardless of intervention protocol . On histological analyses, both preventive and therapeutic intervention treatment protocols improved retention of medial elastin and smooth muscle cells, reduced aortic accumulation of macrophages, T cells and B cells and attenuated aneurysmal mural neovessel formation as compared to non-fasting controls. Additionally, TRF intervention was associated with a transient but significantly slight increase in circulating ketone body levels, without recognizable impact on blood glucose. Conclusion: TRF mitigates experimental AAA progression and related pathologies. These findings suggest that TRF may present an alternative translational approach for medical management of AAA disease.