Impact of apolipoprotein(a) on in vitro angiogenesis
article
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
Topics
Endothelial cellsKringleLp(a)Urinary fragmentsAngiostatinApolipoprotein ABasic fibroblast growth factorFibrinPlasminogenRecombinant proteinTumor necrosis factor alphaUrokinaseAngiogenesisCell proliferationConcentration (parameters)Controlled studyEndothelium cellHuman cellKringle domainLipid analysisProtein expressionProtein secretionAngiogenesis InhibitorsApolipoproteins ACell DivisionCells, CulturedDose-Response Relationship, DrugEndothelium, VascularFibroblast Growth Factor 2HumansMalePeptide FragmentsPlasminogen Activator Inhibitor 1Tumor Necrosis Factor-alphaUrinary Plasminogen Activator
TNO Identifier
236007
ISSN
10795642
Source
Arteriosclerosis, Thrombosis, and Vascular Biology, 21(3), pp. 433-438.
Pages
433-438
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