Penn Cardiovascular Institute Research Directory

Description of CVI Expertise

CVI Program Unit(s):
Lipid / Atherosclerosis / CAD / ACS / Prevention

CVI Research Description:
The major focus of one of our research projects is to identify, characterize and validate biomarkers for the assessment of cardiovascular diseases. By employing proteomicc approaches coupled with state-of-the art stable isotope dilution liquid chromatography/tandem mass spectrometry (LC/MS/MS) we are evaluating the utility of protein modifications as biomarkers of oxidative stress by correlating changes with the development and severity of cardiovascular disease in human populations with defined clinical risks.

Oxidative stress has been proposed as a major cause of vascular injury leading to the development of atherosclerosis. A consequence of oxidative stress is the formation of reactive nitrogen species that specifically modify tyrosine residues in proteins leading to the formation of the unusual amino acid nitrotyrosine. Nitrated proteins have been detected in atherosclerotic lesions and the levels of nitrated proteins in plasma may serve as independent risk association factor for coronary artery disease.

We have also identified several potential plasma protein candidate markers for coronary artery disease and currently we are evaluating in a large cohort of coronary disease patients one of these proteins, nitrated fibrinogen. Studies are also designed to provide insights into the molecular mechanisms of abnormal hemostatic regulation in human coronary heart disease by investigating the biochemical and biophysical alterations in fibrinogen that regulate critical pro- and anti-thrombotic functions of this protein.