Abstract 13182: Cigarette Smoke Induced Atherosclerotic Plaques Drive Aortic Wall Degeneration and Abdominal Aortic Aneurysms

IntroductionExpansion and rupture of abdominal aortic aneurysms (AAA) are clinically associated with high morbidity and mortality. Cigarrete smoke (CS) is the strongest risk factor, yet direct evidence that CS causes AAA is missing. Our aim is to uncover a previously unknown capacity for CS induced-atherosclerosis to directly injure the aorta causing development of AAA.Methods and ResultsHigh cholesterol diet- fed Apoe-/- mice revealed the development of saccular lesions and enlargement of the abdominal aortae of animals exposed to CS twice daily for 5 days per week, but not room air. Lesion incidence increased with duration of cigarette smoke exposure, appearing as early as 4 weeks in the supra-renal abdominal aorta (4% at 4 week, 15% at 8 week and 29% at 12 week; AAA Incidence). Aortic wall rupture resulted in death in 11% of CS exposed mice. Histological examination revealed that aortic wall degenerations were associated with overlying atherosclerotic (AS) plaques (96%) and that the elastic lamina was frequently disrupted in CS exposed mice, even at 4 week time point. BrdU pulse chase and flow cytometry analyses showed more monocytes were recruited in CS exposed aortae. RNA-sequencing of 5159 single cells showed 2 monocyte and 8 macrophage populations were clustered according to considerable differences in gene expression and revealed that hypercholesterolemia determined monocyte and macrophage diversity. Anti colony stimulating factor-1 (αCSF-1) antibody treatment decreased macrophage accumulation and plaque development and led to less damage of the elastic lamina in abdominal aorta, suggesting that macrophages play a critical role in AS and AAA (60% isotype, 19% αCSF-1, p