Atherothrombosis Markers in Diabetics
Schlüsselwörter
Abstrakt
Beschreibung
Atherothrombotic plaques of type 2 diabetic patients are characterized by increased neovascularization and associated intraplaque hemorrhage relative to non-diabetic patients that could account for a major incidence of clinical complications. In parallel, Type 2 diabetic patients are characterized by an increased intracellular oxidative stress in circulating PMNs leading to a primed phenotype. PMN priming could be triggered via their receptor for advanced glycation endproducts. In particular, glycated albumin may activate NADPH oxidase and thus promote the production of reactive oxygen species. Under strong activation, PMNs have been described to release NETs that are constituted by externalized nucleosomes associating DNA, histones and enzymes initially present in granules (such as myeloperoxidase, matrix metalloproteinase 9 or elastase). Our hypothesis is that in diabetic conditions, PMNs could be activated within atherothrombotic plaques and thus represent a trigger for plaque rupture. In the present study, we will evaluate PMN activation in carotid plaques of diabetic vs non-diabetic patients as well as in plasma samples of the same patients. For this purpose, all patients that will undergo carotid surgery by endarterectomy will be enrolled in our study and blood samples will be collected the day before the surgery for preparation of plasma and serum. The endarterectomy sample will be collected, dissected into culprit area of the plaque (CP) and the adjacent non-complicated plaque (NCP), incubated separately in culture medium for 24h at 37°C. The resulting conditioned medium will be aliquoted and stored at -80°C for the different assessments. A representative section of the CP will be saved at the moment of dissection for histological evaluation (presence of neovessels/intraplaque hemorrhage, calcifications, lipids, etc). Markers of neutrophil activation, of intraplaque hemorrhage, of glycation and of oxidative stress will be quantified in both conditioned medium and plasma.
Termine
Zuletzt überprüft: | 08/31/2016 |
Zuerst eingereicht: | 09/07/2016 |
Geschätzte Einschreibung eingereicht: | 09/11/2016 |
Zuerst veröffentlicht: | 09/12/2016 |
Letztes eingereichtes Update: | 09/11/2016 |
Letztes Update veröffentlicht: | 09/12/2016 |
Tatsächliches Startdatum der Studie: | 09/30/2016 |
Geschätztes primäres Abschlussdatum: | 10/31/2018 |
Voraussichtliches Abschlussdatum der Studie: | 05/31/2019 |
Zustand oder Krankheit
Intervention / Behandlung
Other: diabetics
Other: non-diabetics
Phase
Armgruppen
Arm | Intervention / Behandlung |
---|---|
diabetics Type 2 diabetic patients exhibiting fasting glycemia value over 7 mmol/L or glycated hemoglobin value over 6.5% or type 2 diabetic patients under oral anti-diabetic treatment or type 2 diabetic patient under insulin treatment and in which diabetes has been diagnosed after the age of 45 y | Other: diabetics additional blood and urine collection during usual medical care endarterectomy samples during usual medical care |
non-diabetics patients without diagnosed diabetes exhibiting fasting glycemia value under 7 mmol/L | Other: non-diabetics additional blood and urine collection during usual medical care endarterectomy samples during usual medical care |
Zulassungskriterien
Altersberechtigt für das Studium | 18 Years Zu 18 Years |
Studienberechtigte Geschlechter | All |
Probenahmeverfahren | Non-Probability Sample |
Akzeptiert gesunde Freiwillige | Ja |
Kriterien | Inclusion Criteria: - Adult patients with planned endarterectomy - Affiliated to social security rights - Signed inform consent Exclusion Criteria: - pregnancy - Autoimmune disease, chronic inflammatory disease, neoplasia - Type 1 diabetes |
Ergebnis
Primäre Ergebnismaße
1. Neutrophile activation assessed by free DNA levels in atherothrombotic plaques [On day 1 (day of the surgery)]
Sekundäre Ergebnismaße
1. Neutrophile activation assessed by other makers than free DNA levels in atherothrombotic plaques [On day 1 (day of the surgery)]
2. Intraplaque hemorrhage and oxidative stress assessed in plasma and aortic tissue [From day 0 (day before the surgery) to day 1 (day of the surgery)]
3. Correlation between plasma and atherothrombotic plaque markers assessement [From day 0 (day before the surgery) to day 1 (day of the surgery)]
4. Atherothrombosis characterization assessed by histological analysis [On day 1 (day of the surgery)]
Sonstige Ergebnismaßnahmen
1. Banking of biological samples [From day 0 (day before the surgery) to day 1 (day of the surgery)]