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

NCT04502849 | Completed

• 1 other identifier: 25.07
• Study Type: observational
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Atherosclerosis; Endothelial Dysfunction

Keywords

atherosclerosis; endothelial dysfunction; apoptosis; restenosis; atherosclerotic plaque

Outcome Measures

Primary Outcomes (3)

• 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)).

  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)).

  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)).

  Increasing the stage of atherosclerosis (Fontaine classification).

  Up to 2 years after enrollment.

Secondary Outcomes (2)

• Deviations of apoptosis markers in blood and tissue homogenate (Bcl-2, Bax, Fas, VEGF, P53, PDGF-BB) from reference values.

  Up to 2 years after enrollment.

• Deviations of endothelial dysfunction markers in blood (NO metabolites) from reference values..

  Up to 2 years after enrollment.

Study Arms (5)

Group "Bypass" (A)

50 patients with indications for bypass surgery (chronic lower limb ischemia, stage 2b-4 Fontaine).

Procedure: Bypass surgery; Drug: Vitamin E; Diagnostic Test: Duplex ultrasound; Diagnostic Test: Blood sampling; Diagnostic Test: Arterial wall sampling

Group "Endovascular" (B)

50 patients with indications for endovascular angioplasty and stenting (chronic lower limb ischemia, stage 2b-4 Fontaine).

Procedure: Endovascular angioplasty/stenting; Drug: Vitamin E; Diagnostic Test: Duplex ultrasound; Diagnostic Test: Blood sampling

Group "Hybrid" (C)

50 patients with indications for hybrid surgery (endovascular angioplasty/stenting and bypass surgery; chronic lower limb ischemia, stage 2b-4 Fontaine).

Procedure: Hybrid surgery; Drug: Vitamin E; Diagnostic Test: Duplex ultrasound; Diagnostic Test: Blood sampling; Diagnostic Test: Arterial wall sampling

Group "Conservative" (D)

50 patients without indications surgery (conservative treatment, chronic lower limb ischemia, stage 2b-4 Fontaine).

Diagnostic Test: Duplex ultrasound; Diagnostic Test: Blood sampling

Group "Healthy volunteers" (E)

50 healthy subjects.

Diagnostic Test: Duplex ultrasound; Diagnostic Test: Blood sampling

Interventions

Bypass surgery PROCEDURE

Creating a bypass with graft or vein.

Group "Bypass" (A)

Endovascular angioplasty/stenting PROCEDURE

Performing an angioplasty with or without stenting in stenosis.

Group "Endovascular" (B)

Hybrid surgery PROCEDURE

Performing an angioplasty with or without stenting in stenosis and creating a bypass with graft or vein.

Group "Hybrid" (C)

Vitamin E DRUG

100 mg Vitamin E per os 1 per day (1 month).

Also known as: Tocopherol acetate

Group "Bypass" (A); Group "Endovascular" (B); Group "Hybrid" (C)

Duplex ultrasound DIAGNOSTIC_TEST

Duplex ultrasound of lower limbs arteries.

Group "Bypass" (A); Group "Conservative" (D); Group "Endovascular" (B); Group "Healthy volunteers" (E); Group "Hybrid" (C)

Blood sampling DIAGNOSTIC_TEST

Blood sampling for apoptosis and endothelial dysfunction markers.

Group "Bypass" (A); Group "Conservative" (D); Group "Endovascular" (B); Group "Healthy volunteers" (E); Group "Hybrid" (C)

Arterial wall sampling DIAGNOSTIC_TEST

Arterial wall sampling for apoptosis markers.

Group "Bypass" (A); Group "Hybrid" (C)

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with atherosclerotic peripheral arterial disease.

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ryazan State Medical University: lead

Study Sites (1)

Ryazan State Medical University

Ryazan, Russia

Location

MeSH Terms

Conditions

Atherosclerosis; Plaque, Atherosclerotic

Interventions

Coronary Artery Bypass; Stents; Vitamin E; alpha-Tocopherol; Ultrasonography, Doppler, Duplex; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Myocardial Revascularization; Cardiac Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Vascular Grafting; Vascular Surgical Procedures; Thoracic Surgical Procedures; Prostheses and Implants; Equipment and Supplies; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tocopherols; Ultrasonography, Doppler; Ultrasonography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Clinical Laboratory Techniques; Punctures; Investigative Techniques

Study Officials

• Igor A Suchkov, Sc.D.

  Ryazan State Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2020
• First Posted: August 6, 2020
• Study Start: January 1, 2020
• Primary Completion: January 1, 2023
• Study Completion: November 1, 2023
• Last Updated: November 18, 2023

Record last verified: 2022-08

Locations

RU (1)