Oxidative Stress and Arterial Dysfunction in Peripheral Artery Disease

Peripheral artery disease (PAD) is an atherosclerotic disease characterized by a narrowing of the arteries in the lower extremities. Disease manifestations are the result of more than just reduced blood flow, and include endothelial dysfunction, arterial stiffness, and inflammation. Growing evidence suggests that these factors lead to functional impairment and decline in PAD patients. Oxidative stress also plays an important role in the disease, and a growing amount of data suggest a link between arterial dysfunction and oxidative stress. In this review, we present the current evidence for the involvement of endothelial dysfunction, arterial stiffness, and inflammation in the pathophysiology of PAD. We also discuss the links between these factors and oxidative stress, with a focus on nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2)-derived reactive oxygen species (ROS) and decreased nitric oxide (NO) bioavailability. Finally, the potential therapeutic role of NOX2 antioxidants for improving arterial function and functional status in PAD patients is explored.

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Local and Systemic Inflammation and Oxidative Stress After a Single Bout of Maximal Walking in Patients With Symptomatic Peripheral Artery Disease

The Journal of Cardiovascular Nursing ◽

10.1097/jcn.0000000000000686 ◽

2020 ◽

Vol Publish Ahead of Print ◽

Author(s):

Aluisio Andrade-Lima ◽

Natan da Silva Junior ◽

Marcel Chehuen ◽

Roberto Miyasato ◽

Rodrigo W.A. Souza ◽

...

Keyword(s):

Oxidative Stress ◽

Peripheral Artery Disease ◽

Systemic Inflammation ◽

Peripheral Artery ◽

Single Bout ◽

Artery Disease ◽

And Oxidative Stress

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

International Journal of Vascular Medicine ◽

10.1155/2014/160534 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

Andrew W. Gardner ◽

Donald E. Parker ◽

Polly S. Montgomery ◽

Danuta Sosnowska ◽

Ana I. Casanegra ◽

...

Keyword(s):

Oxidative Stress ◽

Growth Factor ◽

Antioxidant Capacity ◽

Peripheral Artery Disease ◽

Control Group ◽

Peripheral Artery ◽

Endothelial Apoptosis ◽

Control Subjects ◽

Artery Disease ◽

And Oxidative Stress

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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The Nitric Oxide System in Peripheral Artery Disease: Connection with Oxidative Stress and Biopterins

Antioxidants ◽

10.3390/antiox9070590 ◽

2020 ◽

Vol 9 (7) ◽

pp. 590

Author(s):

Ahmed Ismaeel ◽

Evlampia Papoutsi ◽

Dimitrios Miserlis ◽

Ramon Lavado ◽

Gleb Haynatzki ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Endothelial Dysfunction ◽

Peripheral Artery Disease ◽

Oxide System ◽

Protein Carbonyls ◽

Nitric Oxides ◽

Peripheral Artery ◽

No Bioavailability ◽

Artery Disease

Peripheral artery disease (PAD) pathophysiology extends beyond hemodynamics to include other operating mechanisms, including endothelial dysfunction. Oxidative stress may be linked to endothelial dysfunction by reducing nitric oxide (NO) bioavailability. We aimed to investigate whether the NO system and its regulators are altered in the setting of PAD and to assess the relationship between NO bioavailability and oxidative stress. Sera from 35 patients with intermittent claudication (IC), 26 patients with critical limb ischemia (CLI), and 35 non-PAD controls were analyzed to determine levels of tetrahydrobiopterin (BH4), dihydrobiopterin (BH2), nitrate/nitrite (nitric oxides, or NOx), arginine, citrulline, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and the oxidative stress markers 8-Oxo-2′-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), advanced glycation end products (AGEs), and protein carbonyls. NOx was significantly lower in IC and CLI patients compared to controls in association with elevated oxidative stress, with the greatest NOx reductions observed in CLI. Compared with controls, IC and CLI patients had reduced BH4, elevated BH2, and a reduced BH4/BH2 ratio. SDMA, the arginine/SDMA ratio, and the arginine/ADMA ratio were significantly higher in CLI patients. The NO system and its regulators are significantly compromised in PAD. This dysregulation appears to be driven by increased oxidative stress and worsens as the disease progresses from claudication to CLI.

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Novel Oral Anticoagulants in Peripheral Artery Disease: Current Evidence

Current Pharmaceutical Design ◽

10.2174/1381612825666181226151959 ◽

2019 ◽

Vol 24 (38) ◽

pp. 4511-4515 ◽

Cited By ~ 1

Author(s):

A. Koutsoumpelis ◽

C. Argyriou ◽

K.M. Tasopoulou ◽

E.I. Georgakarakos ◽

G.S. Georgiadis

Keyword(s):

Peripheral Artery Disease ◽

Oral Anticoagulants ◽

Novel Oral Anticoagulants ◽

Current Evidence ◽

Peripheral Artery ◽

Cardiac Events ◽

Traditional Therapy ◽

Cardiovascular Morbidity And Mortality ◽

Increased Risk ◽

Artery Disease

Background: Peripheral artery disease is a common manifestation of systemic atherosclerosis which strongly correlates to cardiovascular morbidity and mortality. In addition, the progression of peripheral artery disease leads to an increased risk of limb loss. In order to reduce these events, the benchmark of treatment and research over the last years has been the antiplatelet therapy which aims at inhibition of platelet aggregation. Over the last years, new studies combining antiplatelet agents in different therapeutic schemes have been proven efficacious. Unfortunately, patients remain still at high risk of CV events. Novel Oral Anticoagulants have been introduced as alternatives to warfarin, in the prevention and treatment of venous thromboembolism. The rationale of using medication which acts on platelet activation and the coagulation pathway of thrombosis has led investigators to examine the role of Noac's in preventing CV events in patients with peripheral artery disease, stable or unstable. Methods: The aim of this study is to review the current evidence with respect to recently published studies concerning the use of Novel anticoagulants in peripheral artery disease. Results: The Compass trial has shown that a combination of rivaroxaban with traditional therapy may produce promising results in reducing amputation rates, stroke, cardiac events, and mortality, however, there are still safety issues with bleeding requiring acute care. The ePAD study has provided us with insight concerning safety and efficacy after peripheral angioplasty or stenting and actually the need for further research. The Voyager Pad study, following the steps of Compass, is studying the effect and safety of the addition of rivaroxaban to traditional therapy in the highest risk population aka patients undergoing peripheral revascularization. The evidence concerning patients with concomitant atrial fibrillation appears to be insufficient, however, recent guidelines propose the use of novel oral anticoagulants. Conclusion: For the time being, novel oral anticoagulants in combination with aspirin may provide an alternative treatment in PAD, however, it is deemed necessary to identify patient subgroups who will benefit the most.

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Ankle–Brachial Index as an Indicator of Arterial Stiffness in Patients Without Peripheral Artery Disease

Angiology ◽

10.1177/0003319711410307 ◽

2011 ◽

Vol 63 (2) ◽

pp. 150-154 ◽

Cited By ~ 17

Author(s):

Simon W. Rabkin ◽

Siu Him Chan ◽

Colleen Sweeney

Keyword(s):

Arterial Stiffness ◽

Peripheral Artery Disease ◽

Ankle Brachial Index ◽

Peripheral Artery ◽

Artery Disease

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Endovascular treatment of peripheral artery disease is associated with improved central hemodynamics and ventricular function

European Heart Journal ◽

10.1093/ehjci/ehaa946.2381 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

D Messiha ◽

L Halfmann ◽

O Azizy ◽

M Steinmetz ◽

T Rassaf ◽

...

Keyword(s):

Arterial Stiffness ◽

Left Ventricular Function ◽

Endovascular Treatment ◽

Ventricular Function ◽

Peripheral Artery Disease ◽

Cardiovascular Mortality ◽

Left Ventricular ◽

Central Hemodynamics ◽

Peripheral Artery ◽

Artery Disease

Abstract Background Peripheral artery disease (PAD) is a major manifestation of atherosclerosis and a risk factor for morbidity and mortality. PAD itself is associated with increased arterial stiffness with impact on cardiac functions. Previous studies have demonstrated that augmentation index (AIx) and central blood pressure (CBP) correlate with increased cardiovascular mortality. This mechanism has been described as arterio-ventricular (AV) coupling with altered ventricular afterload and a depressed ventricular function, measured by global longitudinal strain (GLS). The impact of PAD-related endovascular treatment on arterial stiffness, central hemodynamics and potential impact on AV coupling has not been elucidated until now. Purpose Aim of the study was to investigate, if endovascular treatment of PAD improves cardiac function via enhanced central hemodynamics and AV coupling. Methods To this aim 77 patients with known symptomatic PAD who underwent interventions in the iliac and femoropopliteal arteries were included in a cross-sectional study. AIx, CBP and GLS were determined using dedicated waveform analysis and echocardiography before and after endovascular treatment. Results Mean age was 65.1±10.4 years with 66.2% male patients. Symptoms were classified by Fontaine classification (stage IIb 80.7%, stage III 5.8% and stage IV 13.5%). Iliac vessel intervention was performed in 16 and femoropopliteal intervention in 61 cases. A stentless approach was feasible in 55 patients with DCB treatment and atherectomy. After endovascular treatment, peripheral perfusion was enhanced (ABI 0.45±0.6 vs 0.81±0.5, p<0.0001). Moreover, central hemodynamics were improved (AIX 33.7±3% vs 27.9±2%, p=0.0008; AP 17.8±2 mmHg vs 14.0±2 mmHg, p=0.0004; central PP 52.4±6 mmHg vs 46.4±6 mmHg, p=0.0001). Impressively, left ventricular function was also significantly improved (GLS −15.7±2.3% vs −17.1±2.8%, p=0.005) with an improvement in AV coupling (PWV/GLS ratio −0.58m/sec% vs −0.56m/sec%, p<0.01). Conclusion Our results demonstrate that endovascular treatment of the peripheral vessels is associated with an improvement of central hemodynamics and left ventricular function via enhanced AV coupling. These prognostic relevant markers of cardiovascular disease could point to an overall potential mortality benefit through PAD treatment. Further investigation of the underlying mechanisms of AV coupling in the setting of endovascular treatment of PAD with impact on cardiovascular mortality is needed in this high-risk population. Funding Acknowledgement Type of funding source: None

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