The Correlation Between the Enzyme Paraoxigenase 1 (PON1) to Carotid Artery Atheromatous Plaque

The objective of the research, is to examine the hypothesis, that the enzyme paraoxygenase 1 ( PON1) can influence carotid artery's atherosclerotic plaque content and stability, and its relation to plasma's enzyme concentration.

Study Overview

• Status: Unknown
• Conditions: Carotid Artery Stenosis
• Intervention / Treatment: Procedure: Carotid endarterectomy

Detailed Description

Atherosclerosis is a major risk factor for morbidity and mortality in the western world. It is characterized by the accumulation of fat (cholesterol) in the arterial wall, creation of the atheromatous plagues and the creation of arterial stenosis and occlusion. The cellular content of theses plaques include: fibroblasts, endothelial cells, smooth muscle cells, macrophages, and lipids: phospholipids, cholesterol, oxysterols and fatty acids. Lipids penetration from the blood stream collaborates different proteins, including the anti-atherogenic enzyme - paraoxygenase 1 - PON1. This enzyme has many ani-atherogenic activities, e.g. Protection from oxygenation and increase of cholesterol efflux from macrophages by HDL. Although the enzyme has a verity of substrates and known anti-atherogenous function, its mechanism is still vogue. The enzymes accumulation rate is the function of the advancement of the fatty strike towards advanced lesion. There is evidence that the presence accumulation and activity of the PON1 within the plaque, is a defense mechanism against atherosclerosis development. The assumption to be proved is that PON1 can control plaque's content and influence its atherogenous factors. Furthermore, we will try to identify these factors that the PON1 acts on. Beside plaque's content and PON1's influence on them, we would like to investigate the phenotype of haptoglobin in the subjects that the plaques were removed from. It is known that diabetics that have the genotype haptoglobin 2-2, characterized by increased risk for oxygenation stress and cardiovascular events (up to 5 times). We would like to examine if there is a correlation between plaque's content, PON1's ability to disassemble oxygenized factors within the plaque, and the phenotype to haptoglobin.

Methods: The plaque source will be from carotid endarterectomy, in the vascular unit. This procedure is a routine operation for patients suffering from carotid artery stenosis, based on clinical decisions. The plaques will be transported to a lipid laboratory soon after they will be harvested, will be frozen in liquid nitrogen and processed into powder. This material will be the origin for the proteins we try to extract. Patient's blood samples (that is drawn routinely for the operation) will be the source for the characterization of the haptoglobin's genotype.

It is critical to emphasize that routinely, the plaques are waste products, and only 5 cc of additional blood is withdrawn from the patients for research purposes.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Tal Salamon, MD; Phone Number: 972-50-8434185; Email: tal.s@ziv.health.gov.il
• Study Contact Backup: Name: Dallit Manheim, MD; Phone Number: 972-50-6265752; Email: DalitMa@clalit.org.il

Study Locations

• Israel
  • Safed, Israel
    • Recruiting
    • Ziv Medical Center
    • Contact: Tal Salamon, MD; Phone Number: 972-50-8434185; Email: tal.s@ziv.health.gov.il
    • Contact: Dallit Manheim, MD; Phone Number: 972-50-6265752; Email: DalitMa@clalit.org.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing CEA

Description

Inclusion Criteria:

• Patients undergoing CEA

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Carotid endarterectomy; Patients that have the common indication for the treatment of carotid artery stenosis by surgery - CEA (carotid endarterectomy), symptomatic and asymptomatic patients.	Procedure: Carotid endarterectomy; The removal of atherosclerotic plaque from the carotid artery, by surgery

Collaborators and Investigators

• Sponsor: Ziv Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Anticipated): October 1, 2012
• Study Completion (Anticipated): October 1, 2014

Study Registration Dates

• First Submitted: September 22, 2011
• First Submitted That Met QC Criteria: September 22, 2011
• First Posted (Estimate): September 23, 2011

Study Record Updates

• Last Update Posted (Estimate): December 16, 2011
• Last Update Submitted That Met QC Criteria: December 15, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: Atherosclerotic plaque; carotid artery; paraoxygenase 1 PON1; Patients undergoing carotid artery endarterectomy CEA for carotid artery stenosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Pathological Conditions, Anatomical; Carotid Artery Diseases; Carotid Stenosis; Plaque, Atherosclerotic
• Other Study ID Numbers: 0032-11-ZIV