Cardiovascular disease is the leading cause of death and accounts for 1 out of every 3 deaths in the United States. Risk factors for cardiovascular disease include high blood pressure, age, and diabetes. Changes in arterial structure occur with age and disease, including an increase in arterial stiffness and changes in structural composition. These structural changes affect the ability of the arteries to perform their primary functions, to transport oxygenated blood through the body and to dampen the pulsatile nature of blood pumped by the heart, and contribute to the development of cardiovascular disease.

The work presented in this dissertation examines the effect of two age- and disease-related chemical processes, oxidation and glycation, on the microstructure and mechanical response of arteries. The mechanical response of arteries is primarily attributed to the structural proteins, collagen and elastin. The mathematical model used to quantify and compare arterial mechanical response was able to differentiate changes in the elastin-dominated vs. collagen-dominated regions of arterial mechanical response. Intact porcine arteries and isolated elastin were oxidized or glycated. Oxidized arteries and oxidized elastin both showed an increase in stiffness compared to untreated samples, while glycated elastin showed a decrease in stiffness. No significant change was observed for the collagen-dominated region of arterial mechanical response. A novel material test system was designed for use with the confocal microscope. This innovative device provided a means of integrating confocal microscope images and mechanical loading information. It was used to analyze changes in collagen and elastin microstructure, and specifically changes in elastin microstructure with oxidation and glycation treatment. Changes in fiber diameter and matrix alignment were observed in oxidized and glycated elastin vs. untreated elastin. Analysis of human artery samples showed increased oxidation and glycation levels with age and changes in mechanical response. Mass spectroscopy (both LC/MS and MALDI-TOF) was employed to examine structural changes in arterial elastin due to oxidation and glycation. This work contributes to our understanding of the age- and disease-related changes in arterial structure and how those changes may affect arterial function. This understanding could help lead to improved prevention and treatment options for cardiovascular disease.