Circulating Anti-Beta2-glycoprotein Antibodies and Endothelial Dysfunction

Study Overview
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Brief Summary
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Circulating anti-beta2-glycoprotein antibodies have been associated with coronary artery disease and peripheral arterial disease. This auto-antibodies could activate endothelial cells leading to the expression of leukocyte adhesion molecules and increasing the release of pro-inflammatory cytokines. On the other hand, endothelial dysfunction of atherosclerotic patients acts as a primary pathogenic event, as it occur before structural changes are evident on angiogram or ultrasound scan. Loss of endothelial normal function causes vasoconstriction, local coagulation alterations and an increase arterial wall proliferation. This situation s been attributed to a reduction in nitric oxide bioactivity, and to an increase oxygen-free radical formation in the context of the pro-inflammatory status found in atherosclerosis. Hypothesis: Circulating Anti-beta2-glycoprotein I antibodies could be associated with endothelial dysfunction and nitric oxide metabolism disruption en patients with peripheral arterial disease.

Official Title
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Influence of Circulating Anti-beta2-glycoprotein I Antibodies on the Endothelial Function and NO Metabolism in Peripheral Arterial Disease Patients.

Conditions
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Peripheral Arterial Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male gender Peripheral arterial disease diagnosis Intermittent claudication. Hemodynamic confirmation of the disease through non-invasive vascular studies. Exclusion Criteria: Autoimmune disease Previous revascularization of the ischemic limb. Ischemic ulcers Previous history of organ transplants. Treatment with immunosuppressors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Atherosclerotic patients<br>Male patients with intermittent claudication. | |
| Control subjects<br>healthy male subjects with normal results on vascular examination and no cardiovascular risk factors, who are not in receipt of any pharmacological treatment, matched by age within two years with peripheral arterial disease patients | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Circulating anti-beta2-glycoprotein I antibodies | The titer of circulating anti-endothelial cell antibodies directed against beta2-glycoprotein antigens (Circulating ABGPI) could be detected by indirect immunofluorescence using a diagnosis reagent kit and subjects serum. | 12 months | 
| Flow-mediated arterial dilatation (FMAD) | FMAD is an ultrasound test based on the ability of endothelial cells to detect changes in shear stress and is one of the most effective and reliable indirect methods for estimating endothelial dysfunction. The ultrasound transducer is applied proximal to the antecubital fossa, and a longitudinal image of the brachial artery is obtained. The basal arterial diameter is determined. A blood pressure cuff is then placed distal to the measurement area and inflated to a pressure of 250 mmHg for five minutes. New measurements of the arterial diameter in the final diastolic phase should be obtained, 60 seconds after the cuff is deflated | 12 months | 
| Nitrite serum levels | Nitrite serum levels reflects the nitric oxide metabolism. Serum nitrite concentration could be measured by colorimetric analysis using the Griess reaction. This is a chemical reaction which uses sulphanilamide and naphthylethylenediamine dihydrochloride under acid conditions (phosphoric acid).The system is capable of detecting nitric oxide in a variety of biological and experimental fluids, like human serum samples. | 12 months | 
| Highly sensitive C-reactive protein. | Highly sensitive C-reactive protein levels could be measured using a highly sensitive, automated immunoassay with the human serum samples. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti-beta2-glycoprotein antibodies, Peripheral arterial disease, Inflammation, Nitric oxide, Endothelial dysfunction