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PMID: 1828468 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Lipoprotein (a) inhibits the generation of transforming growth factor beta: an endogenous inhibitor of smooth muscle cell migration.

The Journal of cell biology ·Vol. 113 ·No. 6 ·1991-06-00 ·Pages 1439-45

Kojima S, Harpel PC, Rifkin DB

Abstract

Conditioned medium (CM) derived from co-cultures of bovine aortic endothelial cells (BAECs) and bovine smooth muscle cells (BSMCs) contains transforming growth factor-beta (TGF-beta) formed via a plasmin-dependent activation of latent TGF-beta (LTGF beta), which occurs in heterotypic but not in homotypic cultures (Sato, Y., and D. B. Rifkin. 1989. J. Cell Biol. 107: 1199-1205). The TGF-beta formed is able to block the migration of BSMCs or BAECs. We have found that the simultaneous addition to heterotypic culture medium of plasminogen and the atherogenic lipoprotein, lipoprotein (a) (Lp(a)), which contains plasminogen-like kringles, inhibits the activation of LTGF-beta in a dose-dependent manner. The inclusion of LDL in the culture medium did not show such an effect. Control experiments indicated that Lp(a) does not interfere with the basal level of cell migration, the activity of exogenous added TGF-beta, the release of LTGF-beta from cells, the activation of LTGF-beta either by plasmin or by transient acidification, or the activity of plasminogen activator. The addition of Lp(a) to the culture medium decreased the amount of plasmin found in BAECs/BSMCs cultures. Similar results were obtained using CM derived from cocultures of human umbilical vein endothelial cells and human foreskin fibroblasts. These results suggest that Lp(a) can inhibit the activation of LTGF-beta by competing with the binding of plasminogen to cell or matrix surfaces. Therefore, high plasma levels of Lp(a) might enhance smooth muscle cell migration by decreasing the levels of the migration inhibitor TGF-beta thus contributing to generation of the atheromatous lesions.

MeSH Terms
Animals Cattle Cell Movement/drug effects Cells, Cultured Lipoprotein(a) Lipoproteins/pharmacology Muscle, Smooth, Vascular/cytology,drug effects,metabolism Plasminogen/pharmacology Transforming Growth Factor beta/biosynthesis,physiology
Chemicals
Lipoprotein(a) Lipoproteins Transforming Growth Factor beta Plasminogen
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kojima S
Department of Cell Biology, New York University Medical School, New York 10016.
Harpel P C
Rifkin D B
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.113.6.1439
Published
1991-06-00
Pages
1439-45
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2289027
Subset
IM
Grants
NCI NIH HHS · CA 23753 · United States
NHLBI NIH HHS · HL-18828 · United States
External Links
PubMed source DOI: 10.1083/jcb.113.6.1439 PMC Full Text View journal details
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