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P47 Understanding endothelial dysfunction in diabetic cardiovascular complications using mass spectrometry-based proteomics
  1. Reema Banarjee1,2,
  2. Akshay Sharma1,
  3. Shakuntala Bai1,
  4. Arati Deshmukh1,
  5. Rubina Kazi1,
  6. Mahesh Kulkarni1
  1. 1Proteomics and Mass Spectrometry Group, CSIR-National Chemical Laboratory, Pune, India
  2. 2School of Molecular and Cellular Biology, University of Leeds, Leeds, UK

Abstract

Introduction One of the initial steps in the development of cardiovascular diseases involves endothelial dysfunction (ED), wherein the regulatory functions of the vascular endothelium are disrupted. ED can be caused by chemically-modified plasma proteins that are present in vivo whose levels are elevated by metabolites and drugs found in the bloodstream. Under conditions such as prolonged hyperglycemia in diabetes, there are elevated plasma levels of glucose-modified or ‘glycated’ proteins, also known as advanced glycation end-products or AGEs. The interaction of these AGEs with their receptor RAGE has been implicated in different complications and could also be a major contributory factor towards the development of ED leading to cardiovascular disease and clinical complications. Since cardiovascular disease is a major pathological outcome in patients that exhibit diabetes, there is importance in understanding the mechanism underlying of how AGEs cause ED. In our study, we have profiled the proteome of endothelial cells stimulated with glycated serum albumin to provide a molecular basis for the development of ED in diabetes.

Methodology Human serum albumin was chemically modified in vitro with glucose and used to stimulate human umbilical vein endothelial cells (HUVECs) in culture to check the effect on their viability and function. Differential total cell proteomics of control and stimulated endothelial cells was performed using mass spectrometry.

Results and conclusion Total cell proteomic analysis shows differential expression of numerous proteins regulating endothelial function including those affecting barrier function, inflammation and angiogenesis. This shows that AGEs can elicit ED, thus predisposing diabetic patients to increased risk of cardiovascular complications.

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