Tsimikas, S. A test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J. Am. Coll. Cardiol. 69, 692–711 (2017).
Article CAS PubMed Google Scholar
Tsimikas, S. et al. NHLBI Working Group recommendations to reduce lipoprotein(a)-mediated risk of cardiovascular disease and aortic stenosis. J. Am. Coll. Cardiol. 71, 177–192 (2018).
Article CAS PubMed PubMed Central Google Scholar
van der Valk, F. M. et al. Oxidized phospholipids on lipoprotein(a) elicit arterial wall inflammation and an inflammatory monocyte response in humans. Circulation 134, 611–624 (2016).
Article PubMed PubMed Central Google Scholar
Kronenberg, F. et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur. Heart J. 22, 3925–3946 (2022).
Clarke, R. et al. Oxidized phospholipids on apolipoprotein B-100 versus plasminogen and risk of coronary heart disease in the PROCARDIS study. Atherosclerosis 354, 15–22 (2022).
Article CAS PubMed Google Scholar
Boffa, M. B. & Koschinsky, M. L. Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease? J. Lipid Res. 57, 745–757 (2016).
Article CAS PubMed PubMed Central 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 PubMed Google Scholar
Etingin, O. R., Hajjar, D. P., Hajjar, K. A., Harpel, P. C. & Nachman, R. L. Lipoprotein (a) regulates plasminogen activator inhibitor-1 expression in endothelial cells. A potential mechanism in thrombogenesis. J. Biol. Chem. 266, 2459–2465 (1991).
Article CAS PubMed Google Scholar
Palabrica, T. 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).
Article CAS PubMed Google Scholar
Helgadottir, A. et al. Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism. J. Am. Coll. Cardiol. 60, 722–729 (2012).
Article CAS PubMed Google Scholar
Kamstrup, P. R., Tybjaerg-Hansen, A. & Nordestgaard, B. G. Genetic evidence that lipoprotein(a) associates with atherosclerotic stenosis rather than venous thrombosis. Arterioscler. Thromb. Vasc. Biol. 32, 1732–1741 (2012).
Article CAS PubMed Google Scholar
Dentali, F. et al. Lipoprotein(a) as a risk factor for venous thromboembolism: a systematic review and meta-analysis of the literature. Semin. Thromb. Hemost. 43, 614–620 (2017).
Article CAS PubMed Google Scholar
Boffa, M. B. et al. Potent reduction of plasma lipoprotein (a) with an antisense oligonucleotide in human subjects does not affect ex vivo fibrinolysis. J. Lipid Res. 60, 2082–2089 (2019).
Article PubMed PubMed Central Google Scholar
Belczewski, A. R. et al. Baboon lipoprotein(a) binds very weakly to lysine-agarose and fibrin despite the presence of a strong lysine-binding site in apolipoprotein(a) kringle IV type 10. Biochemistry 44, 555–564 (2005).
Article CAS PubMed Google Scholar
Tsimikas, S., Moriarty, P. M. & Stroes, E. S. Emerging RNA therapeutics to lower blood levels of Lp(a): JACC focus seminar 2/4. J. Am. Coll. Cardiol. 77, 1576–1589 (2021).
Article CAS PubMed Google Scholar
Kiefer, T. L. & Becker, R. C. Inhibitors of platelet adhesion. Circulation 120, 2488–2495 (2009).
Gurbel, P. A., Jeong, Y. H., Navarese, E. P. & Tantry, U. S. Platelet-mediated thrombosis: from bench to bedside. Circ. Res. 118, 1380–1391 (2016).
Article CAS PubMed Google Scholar
Coughlin, S. R. Protease activated receptors in hemostasis, thrombosis and vascular biology. J. Thromb. Haemost. 3, 1800–1814 (2005).
Article CAS PubMed Google Scholar
Zimmerman, G. A., McIntyre, T. M., Prescott, S. M. & Stafforini, D. M. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit. Care Med. 30, S294–S301 (2002).
Article CAS PubMed Google Scholar
Tsironis, L. D., Mitsios, J. V., Milionis, H. J., Elisaf, M. & Tselepis, A. D. Effect of lipoprotein (a) on platelet activation induced by platelet-activating factor: role of apolipoprotein (a) and endogenous PAF-acetylhydrolase. Cardiovasc. Res. 63, 130–138 (2004).
Article CAS PubMed Google Scholar
Patrono, C. & Baigent, C. Role of aspirin in primary prevention of cardiovascular disease. Nat. Rev. Cardiol. 16, 675–686 (2019).
Malle, E., Ibovnik, A., Stienmetz, A., Kostner, G. M. & Sattler, W. Identification of glycoprotein IIb as the lipoprotein(a)-binding protein on platelets. Lipoprotein(a) binding is independent of an arginyl-glycyl-aspartate tripeptide located in apolipoprotein(a). Arterioscler. Thromb. 14, 345–352 (1994).
Article CAS PubMed Google Scholar
Ezratty, A., Simon, D. I. & Loscalzo, J. Lipoprotein(a) binds to human platelets and attenuates plasminogen binding and activation. Biochemistry 32, 4628–4633 (1993).
Article CAS PubMed Google Scholar
Martinez, C. et al. Binding of recombinant apolipoprotein(a) to human platelets and effect on platelet aggregation. Thromb. Haemost. 85, 686–693 (2001).
Article CAS PubMed Google Scholar
Rand, M. L. et al. Apolipoprotein(a) enhances platelet responses to the thrombin receptor-activating peptide SFLLRN. Arterioscler. Thromb. Vasc. Biol. 18, 1393–1399 (1998).
Article CAS PubMed Google Scholar
Podrez, E. A. et al. Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype. Nat. Med. 13, 1086–1095 (2007).
Article CAS PubMed PubMed Central Google Scholar
Dou, H. et al. Oxidized phospholipids promote NETosis and arterial thrombosis in LNK(SH2B3) deficiency. Circulation 144, 1940–1954 (2021).
Article CAS PubMed PubMed Central Google Scholar
Malle, E. et al. Lysine modification of LDL or lipoprotein(a) by 4-hydroxynonenal or malondialdehyde decreases platelet serotonin secretion without affecting platelet aggregability and eicosanoid formation. Arterioscler. Thromb. Vasc. Biol. 15, 377–384 (1995).
Article CAS PubMed Google Scholar
Boonmark, N. W. & Lawn, R. M. The lysine-binding function of Lp(a). Clin. Genet. 52, 355–360 (1997).
Article CAS PubMed Google Scholar
Barre, D. E. Arginyl-glycyl-aspartyl (RGD) epitope of human apolipoprotein (a) inhibits platelet aggregation by antagonizing the IIb subunit of the fibrinogen (GPIIb/IIIa) receptor. Thromb. Res. 119, 601–607 (2007).
Article CAS PubMed Google Scholar
Bergmark, C. et al. A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma. J. Lipid Res. 49, 2230–2239 (2008).
Article CAS PubMed Google Scholar
Leibundgut, G. et al. Determinants of binding of oxidized phospholipids on apolipoprotein (a) and lipoprotein (a). J. Lipid Res. 54, 2815–2830 (2013).
Article CAS PubMed PubMed Central Google Scholar
Sotiriou, S. N. et al. Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin. FASEB J. 20, 559–561 (2006).
Article CAS PubMed Google Scholar
Morrow, D. A. et al. Vorapaxar in the secondary prevention of atherothrombotic events. N. Engl. J. Med. 366, 1404–1413 (2012).
Article CAS PubMed Google Scholar
Liu, H., Fu, D., Luo, Y. & Peng, D. Independent association of Lp(a) with platelet reactivity in subjects without statins or antiplatelet agents. Sci. Rep. 12, 16609 (2022).
Article PubMed PubMed Central Google Scholar
Byun, Y. S. et al. Relationship of oxidized phospholipids on apolipoprotein B-100 to cardiovascular outcomes in patients treated with intensive versus moderate atorvastatin therapy: the TNT trial. J. Am. Coll. Cardiol. 65, 1286–1295 (2015).
Comments (0)