Role of Endothelial Progenitor Cells Dysregulation and Inflammation in the Pathophysiology of Cardiovascular Complications of Type 2 Diabetes

Type 2 diabetes (T2D) is associated with damage to blood vessels, which can lead to serious complications such as heart disease, stroke, and other vascular problems.

Endothelial progenitor cells (EPCs) help maintain healthy blood vessels by repairing vascular injury. In people with T2D, the number and function of these cells are reduced, which may contribute to poor blood vessel repair and increased cardiovascular risk. The mechanisms responsible for this dysfunction are not fully understood. This study aims to examine how changes in cell signaling and chronic low-grade inflammation in T2D affect EPC function. EPCs will be isolated from patients with T2D, with and without cardiovascular complications, to assess their signaling properties, function, and ability to mature into vascular cells.

An in vitro sub-study will evaluate a potential therapeutic strategy to improve EPC function by increasing the activity of endothelial nitric oxide synthase (eNOS), a protein that plays a key role in maintaining healthy blood vessels. Reduced eNOS activity is an important contributor to vascular dysfunction in diabetes. Enhancing eNOS expression and function in EPCs may improve their regenerative capacity and help prevent or treat diabetic vascular complications.

• Expression levels of angiocrine factor genes in EPCs [Срок оценки: Following the EPC isolation (15-20 days)]
• Cytosolic calcium concetration in EPCs [Срок оценки: Following the EPC isolation (15-20 days)]
• Quantification of Mitochondrial reactive oxygen species (ROS) levels in EPCs [Срок оценки: Following the EPC isolation (15-20 days).]
• Protein Expression of Inflammatory Transcription Factors in Endothelial Progenitor Cells [Срок оценки: Following the EPC isolation (15 - 20 days).]
• Angiogenic Transcription Factor Expression in EPCs [Срок оценки: Time Frame: Following the EPC isolation (15 - 20 days).]
• Proportion of EPCs differentiating into endothelial cells in vitro [Срок оценки: 14 days after initiation of in vitro differentiation.]
• Measurement of eNOS(endothelial nitric oxide synthase)-Dependent Nitric Oxide Production in Endothelial Progenitor Cells [Срок оценки: Following EPC isolation (15-20 days) and 72 hours post-gene transfection.]
• Functional Outcomes of Genetically Enhanced Endothelial Progenitor Cells [Срок оценки: Following EPC isolation (15-20 days) and 72 hours post-gene transfection]