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.
Doulias PT, Tenopoulou M, Greene JL, Raju K, Ischiropoulos H: Nitric oxide regulates mitochondrial fatty acid metabolism through reversible protein S-nitrosylation. Sci Signal 6(256): rs1, Jan 2013.
Thomson L, Tenopoulou M, Lightfoot R, Tsika E, Parastatidis I, Martinez M, Greco TM, Doulias PT, Wu Y, Tang WHW, Hazen SL, Ischiropoulos H: Immunoglobulins against tyrosine-nitrated epitopes in coronary artery disease. Circulation 126(20): 2392-2401, Nov 2012.
Doulias PT, Greene JL, Greco TM, Tenopoulou M, Seeholzer SH, Dunbrack RL, Ischiropoulos H: Structural profiling of endogenous S-nitrosocysteine residues reveals unique features that accommodate diverse mechanisms for protein S-nitrosylation. Proc Natl Acad Sci U S A 107(39): 6958-6963, Sep 2010.
Greco TM, Seeholzer SH, Mak A, Spruce L, Ischiropoulos H: Quantitative mass spectrometry-based proteomics reveals the dynamic range of primary mouse astrocyte protein secretion. J Proteome Res 9(5): 2764-2774, May 2010.
Tsika E, Moysidou M, Guo J, Cushman M, Gannon P, Sandaltzopoulos R, Giasson BI, Krainc D, Ischiropoulos H, Mazzulli JR: Distinct region-specific alpha-synuclein oligomers in A53T transgenic mice: implications for neurodegeneration. J Neurosci 30(9): 3409-3418, Mar 2010.
Parastatidis I, Thomson L, Burke A, Chernysh I, Nagaswami C, Visser J, Stamer S, Liebler DC, Koliakos G, Heijnen HFG, Fitzgerald GA, Weisel JW, Ischiropoulos H: Fibrinogen beta-chain tyrosine nitration is a prothrombotic risk factor. J Biol Chem 283(49): 33846-33853, Dec 2008.
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Last updated: 04/06/2016
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