Abstract

Our central theme is to study non-traditional mechanisms of atherogenesis. The genetic basis and heterogeneity of hyperapoB and its linkage to the apoB, A-I/CIII/AIV gene complex, and lipoprotein lipase genes will be studied. The role of traditional and non-traditional (i.e., DHEAS, homocyst(e)ine, Lp(a) and apoB and A1) risk factors for CAD will be studied in black and white men and women. The biochemical basis of hyperapoB will be studied by elucidating the primary and secondary structures of serum basic proteins (BP) I, II and III and by cloning, sequencing and mapping the cDNAs for BP I, II and III. The specific biochemical mechanism of the acylation stimulatory activity of BP I, II and III and its relation to high affinity binding and uptake in cultured fibroblasts will be studied. Metabolic turnover studies of very low density lipoproteins (VLDL) and the clearance of intestinally-derived lipoproteins and their atherogenicity will be studied in the same normal and hyperapoB subjects. The basis for elevated apoB levels in the Johns Hopkins colony of St. Thomas Hospital (JH-STH) rabbits will be studied by in vivo VLDL turnover studies, secretion and synthesis of apoB in hepatocytes, complex segregation analysis and the use of cDNA clones for the apoB gene; the effect of these parameters, and of cholesterol feeding on atherosclerosis in these animals will be determined. The effect of oxidized LDL and lactosylceramide (LacCer) on the induction of cell proliferation in arterial smooth muscle cells via its effect on UDP-Gal, GlcCer:B1-->4 galactosyltransferase (GalT- 2) and on growth factors will be determined. The role of oxidized LDL, LacCer, triglyceride-rich lipoproteins and cholesterol feeding on endothelial cell dysfunction via the pertussin toxin sensitive G1 transduction pathway will be studied using a porcine bioassay model. Our overall goal is to understand the genetic, biochemical and metabolic factors that regulate non-traditional risk factors for atherosclerosis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL047212-02
Application #
3106932
Study Section
Special Emphasis Panel (SRC (SA))
Project Start
1992-01-01
Project End
1996-11-30
Budget Start
1992-12-01
Budget End
1993-11-30
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Chatterjee, Subroto; Pandey, Ambarish (2008) The Yin and Yang of lactosylceramide metabolism: implications in cell function. Biochim Biophys Acta 1780:370-82
Chatterjee, Subroto; Berliner, Judith A; Subbanagounder, Ganesamoorthy G et al. (2004) Identification of a biologically active component in minimally oxidized low density lipoprotein (MM-LDL) responsible for aortic smooth muscle cell proliferation. Glycoconj J 20:331-8
Juo, S H; Beaty, T H; Duffy, D L et al. (1999) No common major gene for apolipoprotein A-I and HDL3-C levels: evidence from bivariate segregation analysis. Genet Epidemiol 16:54-68
Chatterjee, S; Han, H; Rollins, S et al. (1999) Molecular cloning, characterization, and expression of a novel human neutral sphingomyelinase. J Biol Chem 274:37407-12
Chatterjee, S (1999) Neutral sphingomyelinase: past, present and future. Chem Phys Lipids 102:79-96
Chatterjee, S (1998) Sphingolipids in atherosclerosis and vascular biology. Arterioscler Thromb Vasc Biol 18:1523-33
Lawler Jr, J F; Yin, M; Diehl, A M et al. (1998) Tumor necrosis factor-alpha stimulates the maturation of sterol regulatory element binding protein-1 in human hepatocytes through the action of neutral sphingomyelinase. J Biol Chem 273:5053-9
Kwiterovich Jr, P O; Motevalli, M (1998) Differential effect of genistein on the stimulation of cholesterol production by basic protein II in normal and hyperapoB fibroblasts. Arterioscler Thromb Vasc Biol 18:57-64
Juo, S H; Beaty, T H; Xu, J et al. (1998) Segregation analysis of two-locus models regulating apolipoprotein-A1 levels. Genet Epidemiol 15:73-86
Bhunia, A K; Arai, T; Bulkley, G et al. (1998) Lactosylceramide mediates tumor necrosis factor-alpha-induced intercellular adhesion molecule-1 (ICAM-1) expression and the adhesion of neutrophil in human umbilical vein endothelial cells. J Biol Chem 273:34349-57

Showing the most recent 10 out of 36 publications