Partial amino acid sequence of apolipoprotein(a) shows that it is homologous to plasminogen.

Eaton, Dan; Fless, Gunther M.; Kohr, William J.; McLean, John W.; Xu, Qin-Tu; Miller, Chad G.; Lawn, Richard M.; Scanu, Angelo M.

doi:10.1073/pnas.84.10.3224

Cited by 348 publications

(142 citation statements)

References 28 publications

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“…The amino acid sequence of apolipoprotein(a) has a high degree of homology with plasminogen. Lp(a) contains 37 copies of kringle 4-like, 1 copy of kringle 5-like, and 1 copy of catalytic-like domain of plasminogen [9,10]. Plasminogen is a zymogen that has to be converted into plasmin by plasminogen activators prior to fibrinolysis (see [l l] for review).…”

Section: Introduction 2 Materials and Methodsmentioning

confidence: 99%

Lipoprotein(a) enhances plasma clot lysis in vitro

Mao¹,

Tucci²

1990

FEBS Letters

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Human plasma lipoprotein(a) (Lp(a)) is a macromolecular complex that contams a protem homologous to plasminogen. the precursor of plasmin. We confirmed recent reports that Lp(a) is not activated by streptokinase or tissue plasminogen activator (t-PA) to yreld plasmm-like activtty. In testing the hypothesis that Lp(a) can competittvely inhabit plasma clot lys~s medtated by plasmm, the present study shows that Lp(a) stgmficantly enhanced plasma clot lysis mediated by streptokmase or t-PA The enhancement, however, was not observed in a plasmm-medtated clot lysts usmg a purtfied fibrinogen system. The addttion of x-,-anttplasmm (%-plasmin inhibitor) to thts system inhtbited tibrinolysts: however, no inhibition was observed in the presence of Lp(a). One potential explanation for the Lp(a)-enhanced plasma clot lysis is that Lp(a) neutrahzes the activtty of a,-antiplasmm present m plasma, thereby restormg the acttvtty of plasmm to lyse the clot.Ltpoprotein(a); Plasmmogen; Fibrmolysis; %-Plasmm mhtbttor; a,-Antiplasmin

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Section: Introduction 2 Materials and Methodsmentioning

confidence: 99%

Lipoprotein(a) enhances plasma clot lysis in vitro

Mao¹,

Tucci²

1990

FEBS Letters

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“…Lp(a) contains apo(a), which is attached to apoB through a disulfide bridge. 3 Apo(a) has a high degree of structural similarity to plasminogen, 4 and Lp(a) has been shown to inhibit plasmin formation in vitro. 5 As a result of this effect, Lp(a) inhibits fibrinolysis 5 and accelerates growth of smooth muscle cells 6 in vitro.…”

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confidence: 99%

Increased Degradation of Lipoprotein(a) in Atherosclerotic Compared With Nonlesioned Aortic Intima–Inner Media of Rabbits

Nielsen

Juul

Nordestgaard

1998

ATVB

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Abstract-To investigate a potential role of lipoprotein(a) [Lp(a)] in foam cell formation, we have measured the degradation rates of Lp(a) and LDL in the rabbit aorta in vivo. Lp(a) (or LDL) was labeled with both 131 I-TC and 125 I and injected into 17 rabbits with extensive aortic atherosclerosis and into 16 rabbits without atherosclerosis. As the protein moiety of the doubly labeled lipoproteins is degraded, 131 I-TC is trapped in the cell, whereas 125 I diffuses out of the cell. Twenty-four hours after injection, 12 samples of the aorta and biopsies from 9 other tissues were removed. The degradation rate of Lp(a) (percent of plasma pool per gram tissue per day) was less than that of LDL in the adrenals and in the intestine. In contrast, degradation rates of Lp(a) and LDL were similar in liver, spleen, kidney, heart, lung, skeletal muscle, and adipose tissue. In nonlesioned aortic intima-inner media, the degradation rate of Lp(a) was 39% of that of LDL (t test: P Ͻ.05 in aortic arch and thoracic aorta), whereas the degradation rates of Lp(a) and LDL were similar in atherosclerotic aortic intima-inner media. Lp(a) degradation rates were markedly increased in atherosclerotic compared with nonlesioned aortic intima-inner media: 28.2Ϯ9.2ϫ10 Ϫ7 % and 5.0Ϯ0.6ϫ10 Ϫ7 % of the plasma pool per gram tissue per day in the intima-inner media of the proximal segment of atherosclerotic and nonlesioned aorta, respectively (t test: P Ͻ.01). These results suggest that the metabolism of Lp (a) phospholipids, triglycerides, and apoB. 1 In epidemiological studies, high plasma levels of Lp(a) have been associated with an increased risk of cardiovascular disease. 2 The mechanism by which Lp(a) may promote atherothrombotic disease is unclear, but several possibilities are suggested by the structure of Lp(a). Lp(a) contains apo(a), which is attached to apoB through a disulfide bridge. 3 Apo(a) has a high degree of structural similarity to plasminogen, 4 and Lp(a) has been shown to inhibit plasmin formation in vitro. 5 As a result of this effect, Lp(a) inhibits fibrinolysis 5 and accelerates growth of smooth muscle cells 6 in vitro. Although these effects could promote the development of atherothrombotic disease, the significance needs to be determined in vivo.Because Lp(a) contains cholesterol and cholesterol esters, uptake and degradation of Lp(a) by monocyte-macrophages in the arterial intima could promote foam cell formation, the pathologic hallmark of early atherosclerosis. 7 In vitro evidence suggests that Lp(a) may be taken up and degraded by macrophage-derived foam cells via a cellular receptor distinct from the LDL receptor, scavenger receptors, the LDL receptor-related protein, or plasminogen receptors. 8 -10 Other studies have shown that Lp(a) can be degraded by monocytemacrophages via the LDL receptor and "nonspecific" pathways. [11][12][13][14][15][16] Complex formation by Lp(a) with glycosaminoglycans or modification of Lp(a) with malondialdehyde results in a markedly enhanced uptake and degradation of Lp(a) by monocyte...

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“…Amino acid sequence analysis and cDNA cloning (10,11) have established that apo(a) contains a variable number of kringle domains that share 61-75% homology with kringle 4 of plasminogen. The kringle 4-like repeats of apo(a) are followed by a single copy of plasminogen kringle 5 and a protease domain that shares 94% homology with the corresponding domain of plasminogen.…”

Section: Plasminogen and Apolipoprotein(a): Homologous Proteins With mentioning

confidence: 99%

Structural basis for the pathophysiology of lipoprotein(a) in the athero-thrombotic process

Anglès-Cano

1997

Braz J Med Biol Res

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Lipoprotein Lp(a) is a major and independent genetic risk factor for atherosclerosis and cardiovascular disease. The essential difference between Lp(a) and low density lipoproteins (LDL) is apolipoprotein apo(a), a glycoprotein structurally similar to plasminogen, the precursor of plasmin, the fibrinolytic enzyme. This structural homology endows Lp(a) with the capacity to bind to fibrin and to membrane proteins of endothelial cells and monocytes, and thereby to inhibit plasminogen binding and plasmin generation. The inhibition of plasmin generation and the accumulation of Lp(a) on the surface of fibrin and cell membranes favor fibrin and cholesterol deposition at sites of vascular injury. Moreover, insufficient activation of TGF-ß due to low plasmin activity may result in migration and proliferation of smooth muscle cells into the vascular intima. These mechanisms may constitute the basis of the athero-thrombogenic mode of action of Lp(a). It is currently accepted that this effect of Lp(a) is linked to its concentration in plasma. An inverse relationship between Lp(a) concentration and apo(a) isoform size, which is under genetic control, has been documented. Recently, it has been shown that inhibition of plasminogen binding to fibrin by apo(a) is also inversely associated with isoform size. Specific point mutations may also affect the lysine-binding function of apo(a). These results support the existence of functional heterogeneity in apolipoprotein(a) isoforms and suggest that the predictive value of Lp(a) as a risk factor for vascular occlusive disease would depend on the relative concentration of the isoform with the highest affinity for fibrin. Correspondence

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Partial amino acid sequence of apolipoprotein(a) shows that it is homologous to plasminogen.

Cited by 348 publications

References 28 publications

Lipoprotein(a) enhances plasma clot lysis in vitro

Lipoprotein(a) enhances plasma clot lysis in vitro

Increased Degradation of Lipoprotein(a) in Atherosclerotic Compared With Nonlesioned Aortic Intima–Inner Media of Rabbits

Structural basis for the pathophysiology of lipoprotein(a) in the athero-thrombotic process

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