Apoptosis Proteins and Endothelial Dysfunction in Patients With Atherosclerosis of Peripheral Arteries

November 15, 2023 updated by: Ryazan State Medical University

Comprehensive Assessment of Indices of Apoptosis and Endothelial Dysfunction and Methods of Their Correction in Patients With Atherosclerosis of Peripheral Arteries

Modern vascular surgery has various options for open and endovascular surgical methods aimed at treating patients with peripheral arterial diseases. Despite the achievements of vascular surgery, the occurrence of postoperative complications levels out the success of surgical interventions and requires repeated surgical interventions. The most common complication is stenosis of the reconstruction zone, which develops in approximately 50% of operated patients.

At present, the apoptosis system plays an equally important role in the development of restenosis of the intervention zone. It has been recognized as a central component in the pathogenesis of atherosclerosis, in which the Bcl-2 family of proteins is activated. It is a group of cellular proteins that are important regulators of the apoptosis system in cells located in the mitochondrial membrane. In experimental animal models, it was shown that apoptosis after angioplasty of the coronary arteries proceeds in the form of two waves. After injury to the vascular wall, during the first hours, it is activated in the smooth muscle cells (SMC) of media, and after two weeks in the cells of the neointima, by the 28th day it almost completely stops. A decrease in the apoptosis index in the postoperative period may cause the development of restenosis of the reconstruction zone. The use of antioxidants, for example, alpha-tocopherol acetate, in the first month of the postoperative period, at the time of activation of apoptosis, inhibits the latter and reduces the proliferative activity of the SMC media and neointima. One month after surgery, delayed apoptosis of vascular wall cells can lead to the development of neointima and restenosis. In this case, the use of drugs that enhance apoptosis, for example, lipophilic statins, calcium channel blockers, will be relevant.

Nitric oxide metabolites, depending on the concentration, can act as both an inducer and an inhibitor of apoptosis. The mechanism of NO-induced apoptosis in SMC includes an increase in the Bax / Bcl-2 expression ratio, which leads to the release of cytochrome C from mitochondria, activation of caspase-3 and -9. In patients with atherosclerosis of the peripheral arteries, proteins of the Bcl-2 family and their relationship with markers of endothelial dysfunction have not been sufficiently studied, the results obtained are contradictory.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

250 patients will be divided into 5 groups with follow-up period of 2 years. Blood sampling for apoptosis and proliferation (Bcl-2, Bax, Fas, p53, PDGF-BB (platelet derived growth factor BB), VEGF (vascular endothelial growth factor) and endothelial dysfunction (NO metabolites) markers will be performed before,1 day after, 1 and 6 month after surgery for groups A-C and for groups D, E when included into study.

Arterial wall sampling for apoptosis and proliferation (Bcl-2, Bax, Fas, p53, PDGF-BB, VEGF) during surgery in group A-C patients.

Duplex ultrasound of lower limbs arteries will be performed before,1, 6, 12, 18 and 24 month after surgery for groups A-D and for group E when included into study.

100 mg per os of Vitamin E 1 per day during 1 month after surgery will be prescribed to half of groups A-C patients.

Study Type

Observational

Enrollment (Actual)

250

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Patients with atherosclerotic peripheral arterial disease.

Description

Inclusion Criteria:

  • men or women over 40 years of age;
  • presence of atherosclerotic peripheral artery disease.

Exclusion Criteria:

  • men or women under 40 years of age;
  • chronic lower limb ischemia of a different etiology (disease Burger, aortoarteritis, etc.),
  • active cancer or remission period less than 5 years;
  • decompensated diabetes mellitus;
  • pregnancy or breastfeeding in women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group "Bypass" (A)
50 patients with indications for bypass surgery (chronic lower limb ischemia, stage 2b-4 Fontaine).
Procedure: Bypass surgery
Creating a bypass with graft or vein.
Drug: Vitamin E
100 mg Vitamin E per os 1 per day (1 month).
Other Names:
  • Tocopherol acetate
Diagnostic test: Duplex ultrasound
Duplex ultrasound of lower limbs arteries.
Diagnostic test: Blood sampling
Blood sampling for apoptosis and endothelial dysfunction markers.
Diagnostic test: Arterial wall sampling
Arterial wall sampling for apoptosis markers.
Group "Endovascular" (B)
50 patients with indications for endovascular angioplasty and stenting (chronic lower limb ischemia, stage 2b-4 Fontaine).
Drug: Vitamin E
100 mg Vitamin E per os 1 per day (1 month).
Other Names:
  • Tocopherol acetate
Diagnostic test: Duplex ultrasound
Duplex ultrasound of lower limbs arteries.
Diagnostic test: Blood sampling
Blood sampling for apoptosis and endothelial dysfunction markers.
Procedure: Endovascular angioplasty/stenting
Performing an angioplasty with or without stenting in stenosis.
Group "Hybrid" (C)
50 patients with indications for hybrid surgery (endovascular angioplasty/stenting and bypass surgery; chronic lower limb ischemia, stage 2b-4 Fontaine).
Drug: Vitamin E
100 mg Vitamin E per os 1 per day (1 month).
Other Names:
  • Tocopherol acetate
Diagnostic test: Duplex ultrasound
Duplex ultrasound of lower limbs arteries.
Diagnostic test: Blood sampling
Blood sampling for apoptosis and endothelial dysfunction markers.
Diagnostic test: Arterial wall sampling
Arterial wall sampling for apoptosis markers.
Procedure: Hybrid surgery
Performing an angioplasty with or without stenting in stenosis and creating a bypass with graft or vein.
Group "Conservative" (D)
50 patients without indications surgery (conservative treatment, chronic lower limb ischemia, stage 2b-4 Fontaine).
Diagnostic test: Duplex ultrasound
Duplex ultrasound of lower limbs arteries.
Diagnostic test: Blood sampling
Blood sampling for apoptosis and endothelial dysfunction markers.
Group "Healthy volunteers" (E)
50 healthy subjects.
Diagnostic test: Duplex ultrasound
Duplex ultrasound of lower limbs arteries.
Diagnostic test: Blood sampling
Blood sampling for apoptosis and endothelial dysfunction markers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Restenosis of the reconstruction zone after surgery (detection of narrowing of the lumen of an artery or prosthesis in the reconstruction area using instrumental methods (ultrasound, angiography)).
Time Frame: Up to 2 years after enrollment.
Revealing restenosis after surgery.
Up to 2 years after enrollment.
Thrombosis of the reconstruction zone after surgery (detection of thrombosis in arteries or prosthesis in the reconstruction area using instrumental methods (ultrasound, angiography)).
Time Frame: Up to 2 years after enrollment.
Revealing thrombosis after surgery.
Up to 2 years after enrollment.
Progression of atherosclerosis (detection of narrowing of the lumen of an arteries by atherosclerotic plaque using instrumental methods (ultrasound, angiography)).
Time Frame: Up to 2 years after enrollment.
Increasing the stage of atherosclerosis (Fontaine classification).
Up to 2 years after enrollment.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Deviations of apoptosis markers in blood and tissue homogenate (Bcl-2, Bax, Fas, VEGF, P53, PDGF-BB) from reference values.
Time Frame: Up to 2 years after enrollment.
Deviation of apoptosis markers from reference values.
Up to 2 years after enrollment.
Deviations of endothelial dysfunction markers in blood (NO metabolites) from reference values..
Time Frame: Up to 2 years after enrollment.
Deviation of endothelial dysfunction markers from reference values.
Up to 2 years after enrollment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ryazan State Medical University

Investigators

  • Principal Investigator: Igor A Suchkov, Sc.D., Ryazan State Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2020

Primary Completion (Actual)

January 1, 2023

Study Completion (Actual)

November 1, 2023

Study Registration Dates

First Submitted

July 28, 2020

First Submitted That Met QC Criteria

August 4, 2020

First Posted (Actual)

August 6, 2020

Study Record Updates

Last Update Posted (Estimated)

November 16, 2023

Last Update Submitted That Met QC Criteria

November 15, 2023

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 25.07

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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