Knowledge Bank

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease, characterized by abnormal dilatation of the aorta and remodeling of the elastin and collagen components of the extracellular matrix (ECM). While elastin remodeling is well characterized and is understood to dictate the vessel wall's architecture and stability, little is known about microstructural changes regarding collagen remodeling. This study focuses on identifying characteristics of collagen remodeling in AAA which can eventually be applied to understand pathogenesis and therapeutic techniques in AAA. Studies were conducted on aortic tissue obtained from mouse models of AAA and clinical AAA tissue excised at the time of vascular surgery. Non-AAA control aortic samples from each species were also utilized. Atomic force microscopy (AFM), a high-resolution nanoscale imaging technique was used to observe the sample topography and characterize collagen fibrils. Tissues were also stained using collagen hybridizing peptide (CHP) and analyzed using fluorescent microscopy and second harmonic generation (SHG) microscopy to locate regions of healthy and degraded collagen. Our results indicate that a significant fraction of collagen fibrils in AAA tissues departed from their native structure. These 'abnormal' fibrils had unresolvable D-period bands and a wavier, appearance. AFM analysis revealed a significant reduction in the depth of D-periods in these abnormal fibrils. Additionally, regions of abnormal collagen were located within the remodeled areas of AAA tissue and were distinct from healthy collagen regions as ascertained using CHP staining and SHG. Quantifying the amount of degraded collagen in AAA tissue and understanding the causes of abnormal collagen remodeling can provide novel insights into the ECM remodeling process in AAA and other cardiovascular diseases.