Circulating Anti-Beta2-glycoprotein Antibodies and Endothelial Dysfunction

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

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.

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Disease

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• Spain
  • Madrid
    • Getafe, Madrid, Spain, 28905
      • Hospital Universitario de Getafe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

• Sampling Method: Probability Sample

Study Population

Cases: Male patients with intermittent claudication due to peripheral arterial disease after haemodynamic confirmation of the disease by Doppler and treadmill exercise testing. No previous history of autoimmune disease.

Controls: Healthy male subjects with normal results on vascular examination and no cardiovascular risk factors, who were not in receipt of any pharmacological treatment, matched by age within two years with PAD patients.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Atherosclerotic patients; Male patients with intermittent claudication.
Control subjects; 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?

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

Collaborators and Investigators

• Sponsor: Hospital Universitario Getafe
• Investigators: Principal Investigator: Cesar Varela, MD, Hospital Universitario de Getafe; Study Director: Joaquin De Haro, MD, Hospital Universitario de Getafe; Study Director: Francisco Acin, MD, PhD, Hospital Universitario de Getafe

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: March 26, 2013
• First Submitted That Met QC Criteria: March 28, 2013
• First Posted (Estimate): April 4, 2013

Study Record Updates

• Last Update Posted (Estimate): April 4, 2013
• Last Update Submitted That Met QC Criteria: March 28, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Inflammation; Endothelial dysfunction; Peripheral arterial disease; Nitric oxide; Anti-beta2-glycoprotein antibodies
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: ABGPINO150613