Eric J Belin de Chantemele

Personal Information
Title Associate Professor
Expertise Cardiovascular
Institution Augusta University
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PTP1B, a Potential New Therapeutic Target for Diabetic Vascular Complications
Endothelial dysfunction is characterized by a reduced nitric oxide (NO) bioavailability leading to impaired vasodilation and increased inflammation. Loss of endothelial function is a precursor and major contributor to diabetic vascular complications, which are the most disabling and life-threatening complications of diabetes. Despite numerous clinical trials and therapeutic strategies, preventing and managing endothelial function as well as reducing the occurrence of cardiovascular events remains a challenge in diabetic patients. The goal of the present application is to use a novel and clinically relevant approach consisting of combining the use of human saphenous vein and pulmonary arteries, with cultured primary endothelial cells, to identify potential new therapeutic targets for the treatment of diabetic vascular complications. Preliminary data gathered in human saphenous vein and genetically engineered mice identified Protein tyrosine phosphatase 1B (PTP1B) and endoplasmic reticulum (ER) stress as two potential targets. Based on these findings, we hypothesized that increased PTP1B expression in diabetes causes endothelial dysfunction by inducing insulin resistance and ER stress, in endothelial cells. We will test this hypothesis with the two following aims: 1 - To determine whether diabetes induces a dysfunction of the endothelium secondary to increased PTP1B expression and ER stress in human saphenous vein and pulmonary artery endothelial cells, 2 - To determine whether PTP1B deletion or inhibition protects endothelial cells from diabetes-induced dysfunction by improving insulin sensitivity, reducing ER stress and increasing eNOS functioning. We anticipate that these studies will lead to the identification of the molecular mechanisms by which PTP1B regulates endothelial function. We also expect to demonstrate that PTP1B is a potential target for the treatment of diabetic vascular complications.

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