Understanding Endothelial Dysfunction in Diabetic Cardiovascular Complications Using Mass Spectrometry-based Proteomics

posted Jan 26, 2017, 12:58 AM by sourav ghosh
Mahesh Kulkarni
Proteomics Facility, CSIR-National Chemical Laboratory, Pune, India

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 proteins, also known as advanced glycation end-products (AGEs). The interaction of these AGEs with their receptor RAGE has been implicated in different complications and could also be major contributory factors towards the development of ED in diabetes 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 synthesized AGE-HSA, characterized mass spectrometrically, developed ion library for targeted quantification in the clinical plasma. Furthermore, AGE-HSA was used to study AGE-RAGE signaling in human umbilical vein endothelial cells (HUVECs) cells. Differential total cell proteomics of control and stimulated endothelial cells was performed using mass spectrometry. 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.