Abstract

Lipoprotein (a) (Lp(a) is a form of low density lipoprotein. High levels of Lp(a) are highly correlated with atherosclerotic diseAse but the mechanism is unknown. It is the hypothesis of this application that, in part, this may be attributed to disorders in the fibrinolytic system induced by increased levels of Lp(a). Preliminary studies in this laboratory indicate that Lp(a) is a competitive inhibitor of plasminogen activation, that Lp(a) binds to one type of plasminogen activator, that Lp(a) blocks the binding of plasminogen to its receptor and that in normal subjects and patients with high Lp(a) levels the subunit molecular weight for apo(a) has a different distribution pattern. It is proposed to systematically study: 1) the effect of Lp(a) on plasminogen activation catalyzed by streptokinase-plasmin complexes, urokinase and tissue plasminogen activator; 2) the effect of Lp(a) levels on the binding of plasminogen to endothelial and monocyte-like (U-937) cells; 3) the effect of Lp(a) on the interaction of plasminogen with fibrin. As part of these studies, the direct binding of apo(a) with these cells will also be studied. The effect of Lp(a) on the binding of tissue plasminogen activator to endothelial cells and fibrin will also be examined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL043339-03
Application #
3361964
Study Section
Special Emphasis Panel (SRC (OJ))
Project Start
1989-07-01
Project End
1994-04-30
Budget Start
1991-05-06
Budget End
1992-04-30
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705

  Publications

Smejkal, G B; Snajdar, R M; Hoff, H F (1996) Visualization of unstained protein bands on polyvinylidene fluoride membranes rehydrated in Tween 20. Biotechniques 21:232-3
Cuchacovich, M; Gatica, H; Grigg, D M et al. (1996) Potential pathogenicity of deglycosylated IgG cross reactive with streptokinase and fibronectin in the serum of patients with rheumatoid arthritis. J Rheumatol 23:44-51
Young, T N; Pizzo, S V; Stack, M S (1995) A plasma membrane-associated component of ovarian adenocarcinoma cells enhances the catalytic efficiency of matrix metalloproteinase-2. J Biol Chem 270:999-1002
Young, T N; Rodriguez, G C; Moser, T L et al. (1994) Coordinate expression of urinary-type plasminogen activator and its receptor accompanies malignant transformation of the ovarian surface epithelium. Am J Obstet Gynecol 170:1285-96
Smejkal, G B; Hoff, H F (1994) Cholesterol-specific probe for lipoproteins immobilized on nitrocellulose membranes. Biotechniques 16:68-70
Moser, T L; Young, T N; Rodriguez, G C et al. (1994) Secretion of extracellular matrix-degrading proteinases is increased in epithelial ovarian carcinoma. Int J Cancer 56:552-9
Smejkal, G B; Hoff, H F (1994) Filipin staining of lipoproteins in polyacrylamide gels: sensitivity and photobleaching of the fluorophore and its use in a double staining method. Electrophoresis 15:922-5
Gonzalez-Gronow, M; Gawdi, G; Pizzo, S V (1994) Characterization of the plasminogen receptors of normal and rheumatoid arthritis human synovial fibroblasts. J Biol Chem 269:4360-6
Hoff, H F; O'Neil, J; Yashiro, A (1993) Partial characterization of lipoproteins containing apo[a] in human atherosclerotic lesions. J Lipid Res 34:789-98
Stack, M S; Gray, R D; Pizzo, S V (1993) Modulation of murine B16F10 melanoma plasminogen activator production by a synthetic peptide derived from the laminin A chain. Cancer Res 53:1998-2004

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