News Reader.info

ABSTRACT The extensive homology between apolipoprotein(_a_) and plasminogen has led to the hypothesis that the increased risk for atherosclerosis, cardiac disease and stroke associated with

elevated levels of apolipoprotein(_a_) may reflect modulation of fibrinolysis. We have investigated the role of apolipoprotein(_a_) on clot lysis in transgenic mice expressing the human

apolipoprotein(_a_) gene. These mice develop fatty streak lesions resembling early lesions of human atherosclerosis. Pulmonary emboli were generated in mice by injection, through the right

jugular vein, of a human platelet-rich plasma clot radiolabelled with technetium-99m-labelled antifibrin antibodies. Tissue plasminogen activator was introduced continuously via the right

jugular vein. Clot lysis, determined by _ex vivo_ imaging, was depressed in mice carrying the apolipoprotein(a) transgene relative to their sex-matched normal littermates. These results

directly demonstrate an _in vivo_ effect of apolipoprotein(_a_) on fibrinolysis, an effect that may contribute to the pathology associated with elevated levels of this protein. Access

through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal

Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices

may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support

SIMILAR CONTENT BEING VIEWED BY OTHERS ROLE OF THE ACTIVATION PEPTIDE IN THE MECHANISM OF PROTEIN C ACTIVATION Article Open access 06 July 2020 MILD HYPERLIPIDEMIA IN MICE AGGRAVATES

PLATELET RESPONSIVENESS IN THROMBUS FORMATION AND EXPLORATION OF PLATELET PROTEOME AND LIPIDOME Article Open access 08 December 2020 EFFECT OF ENDOTHELIUM ON THE ANTICOAGULANT ACTIVITY OF A

COVALENT ANTITHROMBIN-HEPARIN COMPLEX Article Open access 27 September 2024 CHANGE HISTORY * _ 01 JUNE 1995 HIV-speciflc cytotoxic T-cells in HIV-exposed but uninfected Gambian women S.

Rowland-Jones, J. Sutton, K. Ariyoshi, T. Dong, F. Gotch, S. Mcadam, D. Whitby, S. Sabally, A. Gallimore, T. Corrah, M. Takiguchi, T. Schultz, Andrew Mcmichael & H. Whittle Nature

Medicine 1, 59–64, 1995. An error in typography resulted in the incorrect printing of m for the Greek character μ. _ REFERENCES * Utermann, G. The mysteries of lipoproteln (a). _Science_

246, 904–910 (1989). Article  CAS  Google Scholar  * Scanu, A.M. & Fless, G.M. Lipoprotein (a): heterogeneity and biological significance. _J. clin. Invest._ 85, 1709–1715 (1990).

Article  CAS  Google Scholar  * Scanu, A.M., Lawn, R.M. & Berg, K. Lipoprotein (a) and atherosclerosis: Davis Conference. _Ann. intern. Med._ 115, 209–218 (1991). Article  CAS  Google

Scholar  * McLean, J.W. _et. al_. Human apolipoprotein (a): cDNA sequence of apolipoprotein (a) is homologous to plasminogen. _Nature_ 300, 132–139 (1987). Article  Google Scholar  * Zysow,

B.R. & Lawn, R.M. The relationship of lipoprotein (a) to hemostasis. _Curr. Opin. Lipidology_ 4, 484–489 (1993). Article  CAS  Google Scholar  * Lawn, R.M. _et. al_. Atherogenesis in

transgenic mice expressing human apolipoprotein (a). _Nature_ 360, 670–672 (1992). Article  CAS  Google Scholar  * Chiesa, G. _et. al_. Reconstitution of lipoprotein (a) by infusion of human

LDL into transgenic mice expressing human apolipoprotein (a). _J. biol. Chem._ 267, 24369–24374 (1992). CAS  PubMed  Google Scholar  * Hajjar, K.A., Gavish, D., Breslow, J.L. & Nachman,

R.L. Lipoprotein (a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis. _Nature_ 339, 303–305 (1989). Article  CAS  Google Scholar  * Stassen,

J.M., Lijnin, H.R., Kieckens, L. & Collen, D. Small animal thrombosis models for the evaluation of thrombolytic agents. _Circulation_, Suppl IV 83, 65–72 (1991). Google Scholar  *

Carmelliet, P. _et. al_. Plasminogen activator inhibitor-1 gene deficient mice. II. Effects on hemostasis, thrombosis and thrombolysis. _J. clin. Invest._ 92, 2756–2760 (1993). Article 

Google Scholar  * Miles, L.A., Fless, G.M., Levin, E.G., Scanu, A.M. & Plow, E.F. A potential basis for the thrombotic risks associated with lipoprotein (a). _Nature_ 339, 301–303

(1989). Article  CAS  Google Scholar  * Edelberg, J.M., Gonzalez-Gronow, M. & Pizzo, S.V. Lipoprotein (a) inhibition of plasminogen activation by tissue-type plasminogen activator.

_Thromb Res_ 57, 155–162 (1990). Article  CAS  Google Scholar  * Loscalzo, J., Weinfeld, M., Fless, G.M. & Scanu, A.M. Lipoprotein (a), fibrin binding, and plasminogen activation.

_Arteriosclerosis_ 10, 240–245 (1990). Article  CAS  Google Scholar  * Liu, J.N., Harpel, P.C., Pannell, R. & Gurewich, V. Lipoprotein (a): A kinetic study of its influence on

fibrin-dependent plasminogen activation by prourokinase or tissue plasminogen activator. _Biochemistry_ 32, 9694–9700 (1993). Article  CAS  Google Scholar  * Leerink, C. _et. al_.

Lysine-binding heterogeneity of Lp (a): Consequences for fibrin binding and inhibition of plasminogen. _Thromb. Haemost._ 68. 185–188 (1992). Article  CAS  Google Scholar  * Halvorsen, S.,

Skjonsberg, O.H., Berg, K., Ruyter, R. & Godal, H.C. Lp (a) lipoprotein inhibit the fibrinolytic system? _Thromb. Res._ 68, 223–232 (1992). Article  CAS  Google Scholar  * Garcia-Frade,

L.J. _et. al_. Fibrinolytic parameters and lipoprotein (a) levels in plasma of patients with coronary artery disease. _Thromb. Res._ 63, 407–418 (1991). Article  CAS  Google Scholar  *

Heinrich, H., Sandkamp, M., Kokott, R., Schulte, H. & Assmann, G. Relationship of lipoprotein (a) to variables of coagulation and fibrinolysis in a healthy population. _Clin. Chem._ 37,

1950–1954 (1991). CAS  PubMed  Google Scholar  * Oshima, S. _et al_. Transient increase of plasma lipoprotein (a) in patients with unstable angina pectoris. Does lipoprotein (a) alter

fibrinolysis. _Arterioscler. Thromb._ 11, 1772–1777 (1991). Article  CAS  Google Scholar  * Glueck, C.J. _et. al_. Relationship between lipoprotein (a), lipids, apolipoproteins, basal and

stimulated fibrinolytic regulators, and D-dimer. _Metabolism_ 42, 236–246 (1993). Article  CAS  Google Scholar  * Scanu, A.M., Praffinger, D., Lee, J.C. & Hinman, J. A single point

mutation (Trp72→Arg) in human apo (a) kringle 4–37 associated with a lysine binding defect in Lp (a). _Biochim. Biophys. Acta._ 1227, 41–45 (1994). Article  CAS  Google Scholar  * von

Hodenberg, E. _et. al_. Effects of lipoprotein (a) on success rate of thrombolytic therapy in acute myocardial infarction. _Am. J. Cardiol._ 67, 1349–1353 (1991). Article  CAS  Google

Scholar  * Moliterno, D.J. _et. al_. Relation of plasma lipoprotein (a) to infarct artery patency in survivors of myocardial infarction. _Circulation_ 88, 935–940 (1993). Article  CAS 

Google Scholar  * Kudryk, B., Rohoza, A., Ahadi, M., Nechtin, J. & Wiebe, M.E. The specificity of a monoclonal antibody for the NH2-terminal region of fibrin. _Molec. Immun._ 21, 89–94

(1984). Article  CAS  Google Scholar  * Rosenbrough, S.F. _et al_ Thrombus imaging with indium-111 and iodine-131-labelled fibrin-specific monoclonal antibody and its F (ab)'2 and Fab

frag. _J. nucl. Med._ 29, 1212–1222 (1988). Google Scholar  Download references AUTHOR INFORMATION Author notes * Barbara C. Furie: Correspondence should be addressed to B.C.F. AUTHORS AND

AFFILIATIONS * Division of Cardiology, New England Medical Center, 750 Washington Street, NEMC #70, Boston, Massachusetts, 02111, USA Theresa M. Palabrica & Mark J. Aronovitz * the

Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts, 02111, USA Theresa M. Palabrica & Mark J. Aronovitz * Falk Cardiovascular Research Center, Division of

Cardiovascular Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California, 94305, USA Alexander C. Liu & Richard M. Lawn * Center for Hemostasis and

Thrombosis Research, Division of Hematology-Oncology, New England Medical Center, 750 Washington Street, NEMC #832, Boston, Massachusetts, 02111, USA Bruce Furie & Barbara C. Furie * the

Departments of Medicine and Biochemistry, Tufts University School of Medicine, Boston, Massachusetts, 02111, USA Barbara C. Furie Authors * Theresa M. Palabrica View author publications You

can also search for this author inPubMed Google Scholar * Alexander C. Liu View author publications You can also search for this author inPubMed Google Scholar * Mark J. Aronovitz View

author publications You can also search for this author inPubMed Google Scholar * Bruce Furie View author publications You can also search for this author inPubMed Google Scholar * Richard

M. Lawn View author publications You can also search for this author inPubMed Google Scholar * Barbara C. Furie View author publications You can also search for this author inPubMed Google

Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Palabrica, T., Liu, A., Aronovitz, M. _et al._ Antifibrinolytic activity of apolipoprotein(a) _in

vivo_: Human apolipoprotein(a) transgenic mice are resistant to tissue plasminogen activator-mediated thrombolysis. _Nat Med_ 1, 256–259 (1995). https://doi.org/10.1038/nm0395-256 Download

citation * Received: 20 October 1994 * Accepted: 20 January 1995 * Published: 01 March 1995 * Issue Date: 01 March 1995 * DOI: https://doi.org/10.1038/nm0395-256 SHARE THIS ARTICLE Anyone

you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the

Springer Nature SharedIt content-sharing initiative