Factors influencing the collagen fiber angle distribution in the mouse aorta.

摘要

The aortic extracellular matrix (ECM) consists of microstructural components, collagen and elastin, along with matrix metalloproteinases (MMPs), which are specialized enzymes that can degrade the matrix as it responds to cellular behaviors such as angiogenesis, apoptosis, proliferation, and migration. Collagen is the most important component among the extracellular proteins because it provides strength and stability to the overall tissue. Changes in collagen content and/or collagen structure play a major role in the development of atherosclerosis. These changes can sometimes be induced by increased or decreased proteinase activity. Therefore, we studied the collagen fiber angle distribution in mouse models of atherosclerosis with or without a deficiency of a selected MMP. Quantification of the collagen fiber data is meaningful in understanding how the diseased aorta maintains homeostasis. Furthermore, such data can be utilized to increase the understanding of disease progression, including but not limited to atherosclerosis and aortic aneurysm.;We characterized collagen fiber angles in mouse models of atherosclerosis which were fed a control chow diet or a high-fat Western diet for 6 months. To visualize collagen, we imaged the mouse thoracic and abdominal aorta using second-harmonic generation (SHG) microscopy. Angle measurements were acquired using a well-established computer software program, Continuity 6.4b. The angle measurements were exported into bivariate histograms. We then designed a multiple regression analysis to compare the distributions of absolute angles between two diet groups, controlling for diet, mouse strain, anatomical location, and radial position in the aortic wall. Data extracted from bivariate histograms were analyzed in R.;In trying to understand the changes seen between chow diet and Western diet fed mice, we began to study physiological variables such as blood pressure and blood flow velocity. We were able to determine that factors beyond atherogenesis, for example aging, influenced aortic collagen fiber angle changes. With aging and atherosclerosis, the extracellular matrix experiences changes in the fibrous structure and content of collagen and elastin. We evaluated changes in collagen content, in particular, collagen type I. To understand the contribution of endothelial cell-derived factors, we performed immunohistochemical studies of endothelial dysfunction, a pathological condition that often accompanies atherosclerosis progression.;This study yielded data of collagen fiber angle distributions throughout the vessel wall in the aortas of mice at different ages and on different diets. We conclude that the aorta displays distinct remodeling responses in the presence of atherogenic stimuli, even in non-lesioned areas.