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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group "Bypass" (A) | 50 patients with indications for bypass surgery (chronic lower limb ischemia, stage 2b-4 Fontaine). |
| |
| Group "Endovascular" (B) | 50 patients with indications for endovascular angioplasty and stenting (chronic lower limb ischemia, stage 2b-4 Fontaine). |
| |
| Group "Hybrid" (C) | 50 patients with indications for hybrid surgery (endovascular angioplasty/stenting and bypass surgery; chronic lower limb ischemia, stage 2b-4 Fontaine). |
| |
| Group "Conservative" (D) | 50 patients without indications surgery (conservative treatment, chronic lower limb ischemia, stage 2b-4 Fontaine). |
| |
| Group "Healthy volunteers" (E) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bypass surgery | Procedure | Creating a bypass with graft or vein. |
| |
| 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)). | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Deviations of apoptosis markers in blood and tissue homogenate (Bcl-2, Bax, Fas, VEGF, P53, PDGF-BB) from reference values. | 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.. |
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Inclusion Criteria:
Exclusion Criteria:
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Patients with atherosclerotic peripheral arterial disease.
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| Name | Affiliation | Role |
|---|---|---|
| Igor A Suchkov, Sc.D. | Ryazan State Medical University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ryazan State Medical University | Ryazan | Russia |
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50 healthy subjects. |
|
| Endovascular angioplasty/stenting |
| Procedure |
Performing an angioplasty with or without stenting in stenosis. |
|
| Hybrid surgery | Procedure | Performing an angioplasty with or without stenting in stenosis and creating a bypass with graft or vein. |
|
| Vitamin E | Drug | 100 mg Vitamin E per os 1 per day (1 month). |
|
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| Duplex ultrasound | Diagnostic Test | Duplex ultrasound of lower limbs arteries. |
|
| Blood sampling | Diagnostic Test | Blood sampling for apoptosis and endothelial dysfunction markers. |
|
| Arterial wall sampling | Diagnostic Test | Arterial wall sampling for apoptosis markers. |
|
Deviation of endothelial dysfunction markers from reference values. |
| Up to 2 years after enrollment. |
| ID | Term |
|---|---|
| D050197 | Atherosclerosis |
| D058226 | Plaque, Atherosclerotic |
| ID | Term |
|---|---|
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D001026 | Coronary Artery Bypass |
| D015607 | Stents |
| D014810 | Vitamin E |
| D024502 | alpha-Tocopherol |
| D018616 | Ultrasonography, Doppler, Duplex |
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D009204 | Myocardial Revascularization |
| D006348 | Cardiac Surgical Procedures |
| D013504 | Cardiovascular Surgical Procedures |
| D013514 | Surgical Procedures, Operative |
| D058017 | Vascular Grafting |
| D014656 | Vascular Surgical Procedures |
| D019616 | Thoracic Surgical Procedures |
| D019736 | Prostheses and Implants |
| D004864 | Equipment and Supplies |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D024505 | Tocopherols |
| D018608 | Ultrasonography, Doppler |
| D014463 | Ultrasonography |
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D011677 | Punctures |
| D008919 | Investigative Techniques |
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