Performance Utility Of Tests For Artherothrombosis

Csako, Gyorgy

Abstract

In analytical studies, we developed and evaluated homogeneous assays for sequential testing of up to four lipid/lipoprotein constituents (HDL-cholesterol, apolipoprotein B, total cholesterol, and triglycerides) in a single tube. These new methods are particularly cost-effective in screening for subjects with high cardiovascular risk. In animal studies, we analyzed the laboratory and morphologic abnormalities in lecithin:cholesterol acyltransferase (LCAT) deficient mice. We showed that these animals develop serum lipoprotein X, glomerulosclerosis, and atherosclerosis and are a useful model of human LCAT deficiency. In a collaborative clinical studies we continued studying atherogenic plasma constituents and markers with respect to their analytical and diagnostic performance and overall clinical utility. In a series of studies, we investigated the effects of estrogen, vitamin E, and the selective estrogen receptor modulator raloxifen on vascular responsiveness, serum lipid profile, and inflammatory vascular markers in postmenopausal women. We observed divergent effects of estrogen hormone replacement therapy on serum markers of inflammation in postmenopausal women with coronary artery disease on appropriate medical management. In other studies dealing with the clinical significance of various viral (e.g., cytomegalovirus, herpes simplex viruses, hepatitis A virus) and bacterial infections (e.g., Helicobacter pylori, Chlamydia pneumoniae) and inflammatory processes in general, we observed that (a) total pathogen burden affects both coronary artery disease risk and serum C-reactive protein levels, and (b) the host response to cytomegalovirus infection is a determinant of susceptibility to coronary artery disease with gender-based differences in inflammation and type of immune response. Further, we found that antibodies to human heat-shock protein 60 are asssociated with the presence and severity of coronary artery disease, indicating an autoimmune component of atherogenesis.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: Clinical Center (CLC)
• Type: Intramural Research (Z01)
• Project #: 1Z01CL010306-03
• Application #: 6543089
• Study Section: (DLM)
• Support Year: 3
• Fiscal Year: 2001

Institution

• Name: Clinical Center
• Country: United States

Publications

Blum, Arnon; Childs, Richard; Smith, Aleah et al. (2009) Targeted antagonism of CXCR4 mobilizes progenitor cells under investigation for cardiovascular disease. Cytotherapy :1-4

Porter, Brian O; Shen, Jean; Kovacs, Joseph A et al. (2009) Interleukin-2 cycling causes transient increases in high-sensitivity C-reactive protein and D-dimer that are not associated with plasma HIV-RNA levels. AIDS 23:2015-9

Lippincott, Margaret F; Carlow, Andrea; Desai, Aditi et al. (2008) Relation of endothelial function to cardiovascular risk in women with sedentary occupations and without known cardiovascular disease. Am J Cardiol 102:348-52

Kling, Mitchel A; Alesci, Salvatore; Csako, Gyorgy et al. (2007) Sustained low-grade pro-inflammatory state in unmedicated, remitted women with major depressive disorder as evidenced by elevated serum levels of the acute phase proteins C-reactive protein and serum amyloid A. Biol Psychiatry 62:309-13

Paul, Jonathan D; Powell, Tiffany M; Thompson, Michael et al. (2007) Endothelial progenitor cell mobilization and increased intravascular nitric oxide in patients undergoing cardiac rehabilitation. J Cardiopulm Rehabil Prev 27:65-73

Vishnyakova, Tatyana G; Kurlander, Roger; Bocharov, Alexander V et al. (2006) CLA-1 and its splicing variant CLA-2 mediate bacterial adhesion and cytosolic bacterial invasion in mammalian cells. Proc Natl Acad Sci U S A 103:16888-93

Baranova, Irina N; Vishnyakova, Tatyana G; Bocharov, Alexander V et al. (2005) Serum amyloid A binding to CLA-1 (CD36 and LIMPII analogous-1) mediates serum amyloid A protein-induced activation of ERK1/2 and p38 mitogen-activated protein kinases. J Biol Chem 280:8031-40

Desai, Ditina; Hasan, Ahmed; Wesley, Robert et al. (2005) Effects of dietary supplements on aspirin and other antiplatelet agents: an evidence-based approach. Thromb Res 117:87-101; discussion 113-5

McGriff-Lee, Nayahmka J; Csako, Gyorgy; Chen, Judy T et al. (2005) Search for predictors of nontherapeutic INR results with warfarin therapy. Ann Pharmacother 39:1996-2002

Eskandari, Farideh; Mistry, Sejal; Martinez, Pedro E et al. (2005) Younger, premenopausal women with major depressive disorder have more abdominal fat and increased serum levels of prothrombotic factors: implications for greater cardiovascular risk. Metabolism 54:918-24