Aortic Regurgitation Dramatically Alters the Distribution of Atherosclerotic Lesions and Enhances Atherogenesis in Mice

Abstract

Objective— Hemodynamics plays a critical role in atherogenesis, but the association between flow pattern and preferential localization of lesion is not fully understood. We developed a mouse model of aortic valve regurgitation (AR) to change the aortic flow pattern and observed the effects on plaque formation. Methods and Results— High-frequency Doppler ultrasound imaging of 10 untreated C57BL/6J mice and 6 sham-treated low-density lipoprotein receptor–deficient ( Ldlr −/− ) mice revealed consistent antegrade blood flow throughout the aorta and oscillatory flow only along the lesser curvature of the aortic arch. Catheter-induced AR in 7 Ldlr −/− mice produced various degrees of diastolic retrograde flow throughout the aorta. After the mice were fed a cholesterol-enriched diet for 6 weeks, the burden of atherosclerotic lesions was increased 6-fold, with the naturally plaque-resistant descending aorta becoming susceptible. The AR severity correlated positively with the lesion burden in the descending thoracic and abdominal aorta but negatively with the lesions in the ascending aorta and aortic arch. Conclusion— This AR model is valuable for elucidating the relationship between hemodynamics and predisposition of the artery wall to atherosclerosis, because of the significant alterations in local flow patterns and the conversion of large regions in the descending aorta from lesion resistant to lesion prone.