Characterization of Post‐Translational Modifications Related to Cardiovascular Disease

Abstract

Unfavorable metabolic conditions (metabolic disorders) associated with obesity and diabetes are major causes for cardiovascular disease. Early detection of the adverse effects of metabolic disease remain elusive. We believe that nonspecific changes which occur in plasma proteins, indicators of inflammation and oxidants, may act as evidence of systemic metabolic disease. Here we elucidate potential biomarkers of CVD including both protein changes and changes in post‐translational modifications (PTMs). Label‐free mass spectrometry‐based proteomics was used to interrogate changes in differential protein and PTM expression in plasma samples from mouse and human models. Label‐free LCMS/MS typically yielded >;1,000 features ( p<0.05, >;2fold). A number of cardiovascular disease related proteins were observed. Up regulated proteins were: haptoglobin, a known biomarker related to inflammation, low mannose binding protein associated with inflammation and CVD in type 2 diabetes, superoxide dismutase and extracellular matrix protein both implicated in type 2 diabetes. We also observed different PTMs associated with oxidative stress including lipid peroxidation products such as hydroxynonenal and multiple forms of oxidation such as cysteine sulfonic acid. Development of a metabolic disorder/CVD‐specific protein panel will afford the first step in biomarker panel development such that disease diagnosis and progression may be performed directly at the molecular level.This project was funded by NIH‐NCRR grants P41 RR010888/ GM104603, S10 RR015942, S10 RR020946, S10 RR025082 and NIH‐NHLBI contract N01 HV00239.