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

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

Interventions

PROCEDURE

Bypass surgery

Creating a bypass with graft or vein.

PROCEDURE

Endovascular angioplasty/stenting

Performing an angioplasty with or without stenting in stenosis.

PROCEDURE

Hybrid surgery

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

DRUG

Vitamin E

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

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.

Sponsors & Collaborators

• Ryazan State Medical University

  lead OTHER

Principal Investigators

• Igor A Suchkov, Sc.D. · Ryazan State Medical University

Eligibility

Min Age

40 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-01-01

Primary Completion

2023-01-01

Completion

2023-11-01

Countries

• Russia

Study Locations