Title
Impact of apolipoprotein(a) on in vitro angiogenesis
Author
Schulter, V.
Koolwijk, P.
Peters, E.
Frank, S.
Hrzenjak, A.
Graier, W.F.
van Hinsbergh, V.W.M.
Kostner, G.M.
Gaubius Instituut TNO
Publication year
2001
Abstract
Angiostatin, which consists of the kringle I-IV domains of plasminogen and which is secreted into urine, is an efficient inhibitor of angiogenesis and tumor growth. Because N-terminal apolipoprotein(a) [apo(a)] fragments, which also contain several types of kringle IV domains, are found in urine as well, we evaluated the potential angiostatic properties of these urinary apo(a) fragments and of a recombinant form of apo(a) [r-apo(a)]. We used human microvascular endothelial cell (hMVEC)-based in vitro assays of tube formation in 3-dimensional fibrin matrixes. Purified urinary apo(a) fragments or r-apo(a) inhibited the basic fïbroblast growth factor/tumor necrosis factor-α-induced formation of capillary-like structures. At concentrations varying from 0.2 to 10 μg/mL, urinary apo(a) fragments inhibited tube formation by as much as 70%, whereas there was complete inhibition by r-apo(a). The highest concentrations of both inhibitors also reduced urokinase plasminogen activator production of basic fibroblast growth factor-induced hMVEC proliferation. The inhibitors had no effect on plasminogen activator inhibitor-1 expression. If our in vitro model for angiogenesis is valid for the in vivo situation as well, our data point toward the possibility that apo(a) may also be physiologically operative in modulating angiogenesis, as the concentration of free apo(a) found in humans exceeds that tested herein. Chemicals/CAS: Angiogenesis Inhibitors; Apolipoproteins A; Fibroblast Growth Factor 2, 103107-01-3; Peptide Fragments; Plasminogen Activator Inhibitor 1; Tumor Necrosis Factor-alpha; Urinary Plasminogen Activator, EC 3.4.21.73
Subject
Health
Endothelial cells
Kringle
Lp(a)
Urinary fragments
Angiostatin
Apolipoprotein A
Basic fibroblast growth factor
Fibrin
Plasminogen
Recombinant protein
Tumor necrosis factor alpha
Urokinase
Angiogenesis
Cell proliferation
Concentration (parameters)
Controlled study
Endothelium cell
Human cell
Kringle domain
Lipid analysis
Protein expression
Protein secretion
Angiogenesis Inhibitors
Apolipoproteins A
Cell Division
Cells, Cultured
Dose-Response Relationship, Drug
Endothelium, Vascular
Fibroblast Growth Factor 2
Humans
Male
Peptide Fragments
Plasminogen Activator Inhibitor 1
Tumor Necrosis Factor-alpha
Urinary Plasminogen Activator
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TNO identifier
236007
ISSN
1079-5642
Source
Arteriosclerosis, Thrombosis, and Vascular Biology, 21 (3), 433-438
Document type
article