Autophagy and Venous Endothelial Function
關鍵詞
抽象
描述
Endothelial dysfunction contributes to different cardiovascular diseases, such as atherosclerosis, myocardial infarction, stroke and peripheral artery diseases. Recent evidence also demonstrated that endothelial dysfunction is associated with vascular venous diseases. In this regard, venous endothelial dysfunction contributes to the development of varicose veins and deep vein thrombosis. Disequilibrium in endothelial function is also present in venous traits derived from saphenous veins which are routinely used as aortocoronary by-pass. The molecular mechanisms involved in venous diseases require further investigations. Autophagy, the intracellular mechanism devoted to the removal of dysfunctional or senescent cytoplasmic elements may represent a new therapeutic target for the treatment of vascular diseases. In this regard, it has been demonstrated that the enhancement of autophagy limits cardiac injury in pre-clinical models of cardiovascular diseases. However, the association between autophagy and vascular disease is still unknown in humans. Spermidine is a natural activator of autophagy which has been demonstrated to extend lifespan in mice and to reduce cardiac dysfunction through autophagy-dependent mechanisms. The objectives of this study will be the following: 1) to test whether spermidine is able to improve vascular function and to reduce oxidative stress in saphenous veins obtained from patients subjected to saphenectomy due to chronic venous insufficiency or varicose veins; 2) to test whether spermidine is able to improve vascular function in saphenous veins derived from patients with atherosclerotic obstructive disease of lower limbs subjected to revascularization through implantation of arteriosus by-pass. In a different set of experiments, the investigators will also test whether vein portions incubated with spermidine show increased autophagy and decreased markers of oxidative stress with respect to controls. The investigators expect that venous segments treated with spermidine will show an amelioration of endothelial function
日期
最後驗證: | 09/30/2019 |
首次提交: | 10/21/2019 |
提交的預估入學人數: | 10/21/2019 |
首次發布: | 10/23/2019 |
上次提交的更新: | 10/23/2019 |
最近更新發布: | 10/27/2019 |
實際學習開始日期: | 11/30/2019 |
預計主要完成日期: | 02/29/2020 |
預計完成日期: | 05/31/2020 |
狀況或疾病
相
手臂組
臂 | 干預/治療 |
---|---|
Group 1 Patients subjected to saphenectomy due to chronic venous insufficiency or varicose veins | |
Group 2 Patients with atherosclerotic obstructive disease of lower limbs |
資格標準
有資格學習的年齡 | 18 Years 至 18 Years |
有資格學習的性別 | All |
取樣方式 | Probability Sample |
接受健康志願者 | 沒有 |
標準 | Inclusion Criteria: - Eligible subjects undergoing saphenectomy - Patients with chronic venous insufficiency - Patients with varicose veins - Eligible subjects undergoing peripheral artery revascularization through implantation of venous by-pass derived from saphenous vein - Acceptance and signature of the informed consent Exclusion Criteria: - Chronic and acute Inflammatory diseases - Immunological and rheumatic diseases - Pre-existing or ongoing neoplasms - Infectious diseases - Previous organ transplantation - Treatment with pharmacological therapies able to modulate autophagy, i. e. rapamycin and derivative compounds (rapalogues). - Antioxidant therapies in the last three months - Patients with surgical technical complications |
結果
主要結果指標
1. Evaluation of endothelial function in venous samples from patients with venous insufficiency before and after treatment with autophagy enhancer spermidine [Immediately after the sampling]
次要成果指標
1. Impact of autophagy on endothelial venous function [6 months]
2. Correlation between autophagy, oxidative stress and endothelial function [6 months]