NCT02898467

Atherothrombosis Markers in Diabetics

Comparison of Atherothrombosis Markers From Aortic Atheroma in Diabetic and Non-diabetic Patients

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 100 (estimated)
• Sponsor: Centre Hospitalier Universitaire de la Réunion · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Intraplaque hemorrhage is the driving force of atherothrombotic plaque vulnerability to rupture and associated clinical complications. Polymorphonuclear neutrophils (PMNs) represent about 70% of leukocytes and may constitute a source of proteases and oxidants that favour plaque rupture. Our objective is to evaluate PMN activation in atherosclerotic plaque of non-diabetic versus type 2 diabetic patients. For this purpose, investigators will quantify the presence of cell-free DNA, that reflect the formation of neutrophil extracellular traps (NETs) in carotid endarterectomy samples.

Detailed description

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.

Conditions

• Diabetes
• Atherothrombosis
• Cardiovascular Disease

Interventions

Type	Name	Description
OTHER	diabetics	additional blood and urine collection during usual medical care endarterectomy samples during usual medical care
OTHER	non-diabetics	additional blood and urine collection during usual medical care endarterectomy samples during usual medical care

Timeline

• Start date: 2016-10-01
• Primary completion: 2018-11-01
• Completion: 2019-06-01
• First posted: 2016-09-13
• Last updated: 2016-09-13

Locations

1 site across 1 country: France