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

Gardner, Andrew W.; Parker, Donald E.; Montgomery, Polly S.; Sоsnowska, Danuta; Casanegra, Ana I.; Esponda, Omar L.; Ungvári, Zoltán; Csiszár, Anna; Sonntag, William E.

doi:10.1177/0003319713501376

Cited by 44 publications

(80 citation statements)

References 57 publications

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“…Epidemiological data relating circulating VEGF concentrations to CVD risk are inconclusive: Blann et al 17 observed elevated blood VEGF levels in patients with coronary or peripheral artery disease compared with healthy controls. Conversely, other investigators have reported decreased serum VEGF levels in patients with peripheral artery disease compared with control subjects 18 19. Taken together, the relation of circulating VEGF concentrations with atherosclerotic disease is unclear at present.…”

Section: Discussionmentioning

confidence: 87%

Circulating vascular endothelial growth factor and the risk of cardiovascular events

Kaess

Preis

Beiser

et al. 2016

Heart

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Section: Discussionmentioning

confidence: 87%

Circulating vascular endothelial growth factor and the risk of cardiovascular events

Kaess

Preis

Beiser

et al. 2016

Heart

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“…In brief, endothelial cells (purchased from Cell Applications, Inc., San Diego, CA, after passage 4; age of the donors is unknown) were initially cultured in MesoEndo Endothelial Cell Growth Medium (Cell Applications, Inc) followed by Endothelial Basal Medium supplemented with 10% fetal calf serum until the time of serum treatment, as described. 31, 32 Inter-individual variance is unlikely to contribute to observed differences because detector cells used for each in vitro study were from the same donor. For treatment, fetal calf serum was replaced with serum (10%; for 24–48 h) collected from our subjects.…”

Section: Methodsmentioning

confidence: 99%

“…For treatment, fetal calf serum was replaced with serum (10%; for 24–48 h) collected from our subjects. 31 Cells cultured in Endothelial Basal Medium supplemented with 10% fetal calf serum served as an additional control.…”

Section: Methodsmentioning

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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“…10 In PAD, exercise is associated with an increase in plasma levels of numerous inflammatory mediators, including thiobarbituric acid-reactive substances (formed as a byproduct of lipid peroxidation), thromboxane, interleukin-8, tumor necrosis factor-α, soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, von Willebrand factor, E-selectin, and thrombomodulin. [87][88][89][90][91][92][93] Inflammatory mediators can aggravate endothelial dysfunction, and markers, such as interleukin-6, are inversely correlated with maximum treadmill performance. 94 When exercise impairment was evaluated by a series of walking tests, higher serum C-reactive protein and serum amyloid A concentrations were associated with reductions in 6-minute-walk distance, 4-meter walking velocity, and a summary performance score that combined performance in walking speed, standing balance, and time for 5 repeated chair rises.…”

Section: Inflammation and Oxidant Stressmentioning

confidence: 99%

“…107 For example, circulating concentrations of vascular endothelial growth factor are decreased in patients with PAD when compared with controls with other comorbid conditions. 93 Innovative anti-inflammatory therapies developed for other indications may have relevance for PAD. For example, intercellular adhesion molecules and vascular cell adhesion molecules play important roles in intracellular signaling and the immune and inflammatory responses and are elevated in patients with PAD.…”

Section: Inflammation and Oxidant Stressmentioning

confidence: 99%

Pathogenesis of the Limb Manifestations and Exercise Limitations in Peripheral Artery Disease

Hiatt¹,

Armstrong²,

Larson³

et al. 2015

Circulation Research

133

118

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P eripheral artery disease (PAD) is initiated by atherogenic mechanisms common to all major vascular territories but encompasses several distinctly important clinical sequelae.1 The global burden of PAD is large and rising, with substantial morbidity and mortality found in high-, middle-, and low-income countries. 2 The atherosclerotic occlusive disease underlying PAD is associated with an exercise limitation in the majority of patients, whereas the classic symptoms of intermittent claudication, ischemic rest pain, and ischemic ulceration are less common manifestations. 3 Patients with PAD are also at increased risk of myocardial infarction, ischemic stroke, heart failure, renovascular hypertension, and vascular death reflecting the systemic atherosclerotic burden. [4][5][6] The epidemiology of Peripheral Artery Disease Compendium© 2015 American Heart Association, Inc. The diagnosis of PAD can be ascertained by simple hemodynamic measurements, in particular, the ankle-brachial index (ABI), a test performed by measuring the systolic blood pressure in each arm and the dorsalis pedis and posterior tibial arteries of each ankle. The highest of the dorsalis pedis or posterior tibial artery pressures is the numerator of the ABI specific to each leg, whereas the highest arm pressure on either side is the denominator. A ratio of <0.90 in either leg is considered hemodynamic evidence of PAD. 16 When imaged, PAD can be characterized as one or more arterial stenoses or occlusions involving the distal aorta, iliac, femoral, popliteal, or tibial arteries. 17The underlying mechanisms responsible for the functional limitations in PAD are hemodynamic in origin, which affects the supply of oxygen and substrates to metabolically active tissue: skeletal muscle in the case of intermittent claudication and skin and subcutaneous tissues in the case of critical leg ischemia. However, additional pathophysiologic mechanisms contribute to the limb manifestations, where a reduction in blood flow alone does not fully account for the exercise limitation. Recent research into the pathophysiology of this exercise limitation has identified several important sequelae resultant from the chronic hemodynamic deficit. These changes affecting the vasculature and skeletal muscle distal to the primary hemodynamic lesions likely contribute to the mechanisms of exercise limitation in PAD. These advances are reviewed here with an additional focus on identifying possible future therapeutic strategies. Symptomatic Manifestations and Exercise Limitations in PADIn the coronary circulation, plaque rupture leading to acute ischemic events is a common clinical presentation; in PAD, progressive atherosclerosis leading to chronic stenosis and occlusion, often in series, in the arteries supplying the lower extremities dominates the symptomatic manifestations.6 Limb SymptomsPatients with PAD may present with a range of limb symptoms. Most patients are either asymptomatic or have atypical limb symptoms during exercise, whereas only a third have typical symptoms of c...

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

Cited by 44 publications

References 57 publications

Circulating vascular endothelial growth factor and the risk of cardiovascular events

Circulating vascular endothelial growth factor and the risk of cardiovascular events

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

Pathogenesis of the Limb Manifestations and Exercise Limitations in Peripheral Artery Disease

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