Cardiovascular disease is the leading cause of death in the United States. As we grow older, our arteries stiffen which decreases its ability to regulate and adapt to blood flow.
My name is Amanda Teo, a senior biomedical science major. I have worked under Dr. Kolega for the past year in the department of pathology and anatomical sciences. His lab focuses on endothelial cells in cardiovascular disease. For the past year, I have been studying the effect of arterial stiffness on endothelial cells.
It is known that arterial stiffness increases with age. According to the American Heart Association, cardiovascular disease is more prevalent among elderly adults. Hence, there is a correlation between arterial stiffness, aging, and cardiovascular disease. However, the nature of how increased arterial stiffness, a major hallmark of cardiovascular disease, modulates endothelial cells production of reactive oxygen species and nitric oxide in response to blood flow is unfamiliar. Therefore, the objective of my project is to compare the production of nitric oxide and reactive oxygen species by endothelial cells on normal physiological and pathological matrix stiffness.
Arteries stiffen with age, decreasing their ability to regulate blood flow. This contributes to cardiovascular disease. Endothelial cells (ECs) sense shear stress created by blood flow and produce nitric oxide (NO) and reactive oxygen species (ROS), which are positive and negative regulators of arterial structure, respectively. I hypothesized that increasing stiffness impairs production of these signals.
To test this, human carotid ECs were cultured on polyacrylamide hydrogels mimicking healthy and aged arterial stiffness, and NO and ROS levels were assessed by Western blotting and fluorescent indicators.
NO levels decreased in ECs on stiff ECM compared to normal, which would impair vascular maintenance in vivo. Unexpectedly, high stiffness also decreased ROS, which would promote endothelial proliferation and growth. However, blood flow affects EC production of NO and ROS, and these measurements were made in static cultures. Ongoing studies examine the effects of stiffness in ECs experiencing physiological flow conditions.
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