Diet‐induced Vascular Remodeling Produces a Shift in Collagen Fiber Angle Distribution in a Mouse Model of Atherosclerosis

Abstract

Atherosclerosis is a chronic inflammatory disease characterized by accumulation of lipids in the artery wall. Clinical complications include plaque rupture, in which thrombosis of the artery can lead to myocardial infarction. In response to plaque development, arteries undergo long-lasting changes in size/composition, termed vascular remodeling. The study objective is to measure collagen fiber angle distribution to understand how the aortic matrix remodels in response to altered mechanical loading resulting from plaque formation. To promote aortic plaque formation, apolipoprotein E (apoE) knockout (KO) and apoE matrix metalloproteinase-12 (MMP12) DKO mice were fed a Western diet for 6 months. Control mice were fed a chow diet. Segments of the thoracic and abdominal aorta were optically sectioned using second harmonic generation (SHG) microscopy to visualize collagen fibers and analyzed using Continuity 6. Multivariate statistical analysis was performed in R to identify variables (mouse strain, diet, aortic position, relative depth in wall) having a significant effect on absolute fiber angle. Our data indicate that the aortas of both apoE KO and apoE MMP12 DKO mice fed Western diet for 6 months undergo a significant shift in collagen fiber angle distribution. This shift coincides with the development of extensive aortic atherosclerosis, suggesting that changes in collagen fiber angle may be part of the vascular remodeling process. We thank Dr. Bruce Gao for use of the SHG microscope. This work was funded by NSF EPS-0903795 and CMMI-1200358.