Background
We compared (a) cellular reactive oxygen species (ROS) production, inflammation, and apoptosis of cultured endothelial cells treated with sera, and (b) circulating inflammatory, antioxidant capacity, vascular biomarkers, and calf muscle hemoglobin oxygen saturation (StO2) in men and women with PAD. A secondary aim was to compare exercise performance and daily ambulatory activity between men and women. We hypothesized that women would have more impaired endothelial cellular ROS, inflammation, and apoptosis than men, as well as worse systemic inflammation, antioxidant capacity, vascular biomarkers, calf muscle StO2, exercise performance, and daily ambulatory activity.
Methods
One hundred forty-eight symptomatic men and women with PAD were characterized on the endothelial effects of circulating factors present in the sera using a cell culture-based bioassay on primary human arterial endothelial cells. Patients were further evaluated on circulating inflammatory and vascular biomarkers, physical examination and medical history, exercise performance, calf muscle StO2 during exercise, and ambulatory activity monitored during one week.
Results
Cellular ROS production was higher in African-American women than in men (p = 0.021), but there was no gender difference in Caucasians (p = 537). Men and women were not significantly different on endothelial cell apoptois (p = 833) and NF-κB activity (p = 0.465). For circulating factors, additional gender differences were found when comparisons were made within each race. In African-Americans, women had higher intercellular cell adhesion molecule-1 (p = 0.022) and leptin (p < 0.001), whereas in Caucasians, women had higher matrix metallopeptidase 9 (p = 0.047), higher vascular cell adhesion molecule-1 (p = 0.047), and lower hepatocyte growth factor (p = 0.046). Overall, women had higher apolipoprotein CIII (p = 0.035), lower pain-free distance (p = 0.048) and total distance (p < 0.001) during the 6-minute walk test, shorter time for calf muscle StO2 to reach the minimum value during exercise (p = 0.027), and slower average cadence (p = 0.004) during daily ambulation.
Conclusions
African-American women with symptomatic PAD have a heightened oxidative status likely resulting in increased endothelial oxidative stress than men. Furthermore, women exhibit a more pronounced pro-inflammatory profile of circulating biomarkers than men, as well as more limited peripheral microcirculation, exercise performance, and ambulatory activity than men. The clinical significance is that women with symptomatic PAD are in greater need of clinical intervention to improve oxidative stress, inflammation, and microcirculation than men, which may, in turn, favorably impact their lower exercise performance and daily activity.