Lipoprotein(a), plasmin modulation, and atherogenesis.
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.
Harpel
P C
PC
Department of Medicine, Mount Sinai Medical Center, New York, NY 10029, USA.
Hermann
A
A
Zhang
X
X
Ostfeld
I
I
Borth
W
W
D000328:Adult; D000818:Animals; D001161:Arteriosclerosis / Q000097:blood* / Q000473:pathology; D002455:Cell Division; D002648:Child; D005337:Fibrin / Q000502:physiology*; D005341:Fibrinolysin / Q000502:physiology*; D000882:Haplorhini; D006801:Humans; D018082:Kringles / Q000502:physiology; D017270:Lipoprotein(a) / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D010958:Plasminogen / Q000737:chemistry / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D017270:Lipoprotein(a); D016212:Transforming Growth Factor beta; D005337:Fibrin; D010958:Plasminogen; D005341:Fibrinolysin