Relationship Between Noninvasively Measured Endothelial Function and Peripheral Arterial Disease

Maldonado, Francisco José Medina; Haro, Joaquín De; Aguilar, Esther Martínez; González, A. Flórez; García, J.R. March; García, Francisco Acín

doi:10.1177/0003319708327787

Cited by 27 publications

(24 citation statements)

References 35 publications

(64 reference statements)

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“…The higher pro-oxidative status of women is in line with the results of our previous study in which women had lower small artery elasticity index than men, and African-Americans had lower small artery elasticity indices than Caucasians. 19 The fact that higher endothelial cell ROS production of women was found in African-Americans but not in Caucasians suggests that African-American women represent a subgroup of patients with PAD who are particularly susceptible to progression of atherosclerosis, 34 and increased risk of coronary events. 34, 35 …”

Section: Discussionmentioning

confidence: 99%

Gender and racial differences in endothelial oxidative stress and inflammation in patients with symptomatic peripheral artery disease

Gardner

Parker

Montgomery

et al. 2015

Journal of Vascular Surgery

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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.

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Section: Discussionmentioning

confidence: 99%

Gender and racial differences in endothelial oxidative stress and inflammation in patients with symptomatic peripheral artery disease

Gardner

Parker

Montgomery

et al. 2015

Journal of Vascular Surgery

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“…15, 17, 21–23 We 24 and others 21 have found that endothelial function is impaired in PAD subjects. Furthermore, co-morbid conditions and cardiovascular risk factors are highly prevalent in subjects with PAD, such as metabolic syndrome, 25 diabetes, 2, 3 hypertension, 2, 3 dyslipidemia, 2, 3 smoking, 2, 3 ambulatory dysfunction 7, 8 and low physical activity levels.…”

Section: Introductionmentioning

confidence: 88%

Impaired Vascular Endothelial Growth Factor A and Inflammation in Patients With Peripheral Artery Disease

et al. 2013

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We compared apoptosis, cellular oxidative stress, and inflammation of cultured endothelial cells treated with sera from 130 subjects with peripheral artery disease (PAD) and 36 control subjects with high burden of co-morbid conditions and cardiovascular risk factors. Secondly, we compared circulating inflammatory, antioxidant capacity, and vascular biomarkers between the groups. The groups were not significantly different (p>0.05) on apoptosis, hydrogen peroxide, hydroxyl radical antioxidant capacity, and nuclear factor k-light-chain-enhancer of activated B cells. Circulating tissue necrosis factor alpha (TNFα) (p=0.016) and interleukin-8 (p=0.006) were higher in the PAD group, whereas vascular endothelial growth factor-A (VEGF-A) (p=0.023) was lower. PAD does not impair the endothelium beyond that which already occurs from co-morbid conditions and cardiovascular risk factors in subjects with claudication. However, subjects with PAD have lower circulating VEGF-A than controls, and higher circulating inflammatory parameters of TNFα and IL-8.

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“…Endothelial dysfunction is an early marker of vascular dysfunction prior to the development of structural changes and clinical symptoms [15–21], contributes to the progression of atherosclerosis [21], and increases the risk of coronary events [15, 17, 21–23]. We [24] and others [21] have found that endothelial function, as measured by the criterion method of brachial artery flow-mediated dilation, is impaired in PAD subjects.…”

Section: Introductionmentioning

confidence: 99%

“…We [24] and others [21] have found that endothelial function, as measured by the criterion method of brachial artery flow-mediated dilation, is impaired in PAD subjects. Apoptosis, cellular oxidative stress, and inflammation of the endothelium are factors that may contribute to the impaired endothelial function of subjects with PAD.…”

Section: Introductionmentioning

confidence: 99%

Greater Endothelial Apoptosis and Oxidative Stress in Patients with Peripheral Artery Disease

Gardner

Parker

Montgomery

et al. 2014

International Journal of Vascular Medicine

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We compared apoptosis, cellular oxidative stress, and inflammation of cultured endothelial cells treated with sera from 156 subjects with peripheral artery disease (PAD) and 16 healthy control subjects. Furthermore, we compared circulating inflammatory, antioxidant capacity, and vascular biomarkers between the two groups. The PAD group had a 164% higher value for endothelial cell apoptosis (P < 0.001) and a 62% higher value for endothelial cellular reactive oxygen species production (P < 0.001) than the control group. Furthermore, the PAD group had lower systemic antioxidant capacity measured by hydroxyl radical antioxidant capacity activity (P < 0.001), higher inflammatory and vascular measures of high-sensitivity C-reactive protein (P < 0.001), interleukin-8 (P < 0.001), serum amyloid A (P < 0.001), vascular cell adhesion molecule-1 (P < 0.001), adiponectin (P < 0.001), apolipoprotein B (P = 0.013), apolipoprotein CIII (P = 0.035), lower vascular endothelial growth factor-A (P < 0.001), and hepatocyte growth factor (P < 0.001) than the control group. Subjects with PAD have greater endothelial apoptosis and oxidative stress than control subjects with low burden of comorbid conditions and cardiovascular risk factors. Furthermore, subjects with PAD have lower systemic antioxidant capacity and angiogenic measures and higher circulating inflammatory parameters.

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Relationship Between Noninvasively Measured Endothelial Function and Peripheral Arterial Disease

Abstract: Patients with PAD present endothelial dysfunction, but this does not seem to determine the severity of the disease.

Cited by 27 publications

References 35 publications

Gender and racial differences in endothelial oxidative stress and inflammation in patients with symptomatic peripheral artery disease

Gender and racial differences in endothelial oxidative stress and inflammation in patients with symptomatic peripheral artery disease

Impaired Vascular Endothelial Growth Factor A and Inflammation in Patients With Peripheral Artery Disease

Greater Endothelial Apoptosis and Oxidative Stress in Patients with Peripheral Artery Disease

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