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

[hapyman]

I've been targeting Lp(a) due to recent research over at IHs. Here is some interesting info that it inhibits the generation of TGF-B. Thought you might like this one Chore Boy

Lipoprotein (a) inhibits the generation of transforming growth factor beta: an endogenous inhibitor of smooth muscle cell migration.
Kojima S, Harpel PC, Rifkin DB.

Department of Cell Biology, New York University Medical School, New York 10016.

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.

[hapyman]

Also Lp(a) can inhibit the formation of plasmin, which is necessary to break down fibrotic clots and thus leads to fibrosis.

Lipoprotein(a), plasmin modulation, and atherogenesis.
Harpel PC, Hermann A, Zhang X, Ostfeld I, Borth W.

Department of Medicine, Mount Sinai Medical Center, New York, NY 10029, USA.

Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein however the mechanisms by which Lp(a) promote the atherosclerotic process are not clear. The apolipoprotein(a) portion of Lp(a) shares partial homology with plasminogen, a finding that has stimulated numerous studies. Lp(a) binds to fibrin and the affinity between fibrin surfaces and Lp(a) appears to be related to the state of oxidation of the lipoprotein particle. Lp(a) also effects fibrin-dependent plasminogen activation. Recent findings suggest that dependent plasminogen activation. Recent findings suggest that depending upon the in vitro conditions, Lp(a) either promotes or inhibits plasmin formation. Lp(a) also inhibits cell-surface dependent plasmin generation that is associated with an inhibition of transforming growth factor-beta (TGF-beta) production in cell coculture systems. Lp(a) stimulates smooth muscle cell migration and proliferation as a secondary response to this decrease in TGF-beta concentration. Studies in transgenic mice containing the human apolipoprotein(a) gene, document that both plasmin and TGF-beta formation in the media of the aorta is markedly decreased in the presence of apo(a). Thus the atherogenicity of Lp(a) may be mediated, in part, through its modulation of plasmin and TGF-beta production in the blood vessel wall.

[chore boy]

Thanks.