Ignite Creation Date:
2024-05-06 @ 3:03 PM
Last Modification Date:
2024-10-26 @ 1:41 PM
Study NCT ID:
NCT04502849
Status:
COMPLETED
Last Update Posted:
2023-11-18
First Post:
2020-07-28
Brief Title:
Apoptosis Proteins and Endothelial Dysfunction in Patients With Atherosclerosis of Peripheral Arteries
Sponsor:
Ryazan State Medical University
Organization:
Ryazan State Medical University
Study Overview
Official Title:
Comprehensive Assessment of Indices of Apoptosis and Endothelial Dysfunction and Methods of Their Correction in Patients With Atherosclerosis of Peripheral Arteries
Status:
COMPLETED
Status Verified Date:
2022-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
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 before1 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 before1 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
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 before1 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None