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Thrombosis, Inflammation, and Lipoprotein(a): Clinical Implications

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Lipoprotein(a)

Part of the book series: Contemporary Cardiology ((CONCARD))

Abstract

Multiple mechanisms mediate thrombus formation, including activation of platelets, coagulation, and fibrinolysis. This chapter discusses the complexity of interactions between lipoprotein(a) (Lp(a)), coagulation, fibrinolytic, and inflammatory factors. Lp(a), apo(a), and its fragments can bind to the extracellular matrix of arterial and venous walls. Elevated levels of Lp(a) mediate thrombus formation and slow plasmin generation, while apo(a) can inactivate tissue factor pathway inhibitor promoting blood coagulation. Changing conditions of blood flow and high shear stress impact the interplay between thrombus development in the arterial and venous systems. Oxidation of Lp(a) increases clot density. The oxidized phospholipids (oxPL)-Lp(a) complex has been shown to upregulate adhesion molecules, increase secretion of chemo-attractants and cytokines, interact with various signal transduction receptors on the cell surface, and modulate binding of leukocytes to endothelial cells. Smaller apo(a) isoforms demonstrate stronger association with oxPL. In this chapter, we review clinical relevance and implications of pro-thrombotic and pro-inflammatory states associated with Lp(a). Further investigation of the role of Lp(a)-targeted therapies in mediating levels of pro-inflammatory, pro-thrombotic, and antifibrinolytic markers and their effects on clinical outcomes is needed.

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References

  • Akaike M, Azuma H, Kagawa A, et al. Effect of aspirin treatment on serum concentrations of lipoprotein(a) in patients with atherosclerotic diseases. Clin Chem. 2002;48:1454–9.

    CAS  PubMed  Google Scholar 

  • Angles-Cano E, de la Pena DA, Loyau S. Inhibition of fibrinolysis by lipoprotein(a). Ann N Y Acad Sci. 2001;936:261–75.

    CAS  PubMed  Google Scholar 

  • Berliner JA, Leitinger N, Tsimikas S. The role of oxidized phospholipids in atherosclerosis. J Lipid Res. 2009;50(Suppl):S207–12.

    PubMed  PubMed Central  Google Scholar 

  • Bezemer ID, van der Meer FJ, Eikenboom JC, Rosendaal FR, Doggen CJ. The value of family history as a risk indicator for venous thrombosis. Arch Intern Med. 2009;169:610–5.

    PubMed  Google Scholar 

  • Boffa MB, Koschinsky ML. Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease? J Lipid Res. 2016;57:745–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Boffa MB, Marcovina SM, Koschinsky ML. Lipoprotein(a) as a risk factor for atherosclerosis and thrombosis: mechanistic insights from animal models. Clin Biochem. 2004;37:333–43.

    CAS  PubMed  Google Scholar 

  • Boonmark NW, Lou XJ, Yang ZJ, et al. Modification of apolipoprotein(a) lysine binding site reduces atherosclerosis in transgenic mice. J Clin Invest. 1997;100:558–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brown MS, Goldstein JL. Plasma lipoproteins: teaching old dogmas new tricks. Nature. 1987;330:113–4.

    CAS  PubMed  Google Scholar 

  • Brugemann J, van der Meer J, Hillege HL, et al. Lipoprotein(a) levels in patients with myocardial infarction treated with anistreplase: no prediction of efficacy but inverse correlation with plasminogen activation in non-patency. Int J Cardiol. 1994;45:109–13.

    CAS  PubMed  Google Scholar 

  • Caplice NM, Panetta C, Peterson TE, et al. Lipoprotein (a) binds and inactivates tissue factor pathway inhibitor: a novel link between lipoproteins and thrombosis. Blood. 2001;98:2980–7.

    CAS  PubMed  Google Scholar 

  • Chasman DI, Shiffman D, Zee RY, et al. Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy. Atherosclerosis. 2009;203:371–6.

    CAS  PubMed  Google Scholar 

  • Danik JS, Buring JE, Chasman DI, Zee RY, Ridker PM, Glynn RJ. Lipoprotein(a), polymorphisms in the LPA gene, and incident venous thromboembolism among 21483 women. J Thromb Haemost. 2013;11:205–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dentali F, Gessi V, Marcucci R, Gianni M, Grandi AM, Franchini M. Lipoprotein(a) as a risk factor for venous thromboembolism: a systematic review and meta-analysis of the literature. Semin Thromb Hemost. 2017;43:614–20.

    CAS  PubMed  Google Scholar 

  • Di Maio S, Lamina C, Coassin S, et al. Lipoprotein(a) and SARS-CoV-2 infections: Susceptibility to infections, ischemic heart disease and thromboembolic events. J Intern Med. 2021; https://doi.org/10.1111/joim.13338.

  • Edelberg JM, Pizzo SV. Lipoprotein (a) promotes plasmin inhibition by alpha 2-antiplasmin. Biochem J. 1992;286(Pt 1):79–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Edelberg JM, Pizzo SV. Lipoprotein (a) in the regulation of fibrinolysis. J Atheroscler Thromb. 1995;2(Suppl 1):S5–7.

    CAS  PubMed  Google Scholar 

  • Edelberg JM, Gonzalez-Gronow M, Pizzo SV. Lipoprotein a inhibits streptokinase-mediated activation of human plasminogen. Biochemistry. 1989;28:2370–4.

    CAS  PubMed  Google Scholar 

  • Emdin CA, Khera AV, Natarajan P, et al. Phenotypic characterization of genetically lowered human lipoprotein(a) levels. J Am Coll Cardiol. 2016;68:2761–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Espinosa G, Tassies D, Font J, et al. Antiphospholipid antibodies and thrombophilic factors in giant cell arteritis. Semin Arthritis Rheum. 2001;31:12–20.

    CAS  PubMed  Google Scholar 

  • Etingin OR, Hajjar DP, Hajjar KA, Harpel PC, Nachman RL. Lipoprotein (a) regulates plasminogen activator inhibitor-1 expression in endothelial cells. A potential mechanism in thrombogenesis. J Biol Chem. 1991;266:2459–65.

    CAS  PubMed  Google Scholar 

  • Ezhov M, Safarova M, Afanasieva O, Mitroshkin M, Matchin Y, Pokrovsky S. Matrix metalloproteinase 9 as a predictor of coronary atherosclerotic plaque instability in stable coronary heart disease patients with elevated lipoprotein(a) levels. Biomolecules. 2019;9(4):129. https://doi.org/10.3390/biom9040129.

  • Ezratty A, Simon DI, Loscalzo J. Lipoprotein(a) binds to human platelets and attenuates plasminogen binding and activation. Biochemistry. 1993;32:4628–33.

    CAS  PubMed  Google Scholar 

  • Falco C, Estelles A, Dalmau J, Espana F, Aznar J. Influence of lipoprotein (a) levels and isoforms on fibrinolytic activity—study in families with high lipoprotein (a) levels. Thromb Haemost. 1998;79:818–23.

    CAS  PubMed  Google Scholar 

  • Garcia-Arguinzonis M, Diaz-Riera E, Pena E, et al. Alternative C3 complement system: lipids and atherosclerosis. Int J Mol Sci. 2021;22:5122.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Goldenberg NA, Bernard TJ, Hillhouse J, et al. Elevated lipoprotein (a), small apolipoprotein (a), and the risk of arterial ischemic stroke in North American children. Haematologica. 2013;98:802–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Grainger DJ, Kirschenlohr HL, Metcalfe JC, Weissberg PL, Wade DP, Lawn RM. Proliferation of human smooth muscle cells promoted by lipoprotein(a). Science. 1993;260:1655–8.

    CAS  PubMed  Google Scholar 

  • Gregson J, Kaptoge S, Bolton T, et al. Cardiovascular risk factors associated with venous thromboembolism. JAMA Cardiol. 2019;4:163–73.

    PubMed  Google Scholar 

  • Hajjar KA, Gavish D, Breslow JL, Nachman RL. Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis. Nature. 1989;339:303–5.

    CAS  PubMed  Google Scholar 

  • Hancock MA, Boffa MB, Marcovina SM, Nesheim ME, Koschinsky ML. Inhibition of plasminogen activation by lipoprotein(a): critical domains in apolipoprotein(a) and mechanism of inhibition on fibrin and degraded fibrin surfaces. J Biol Chem. 2003;278:23260–9.

    CAS  PubMed  Google Scholar 

  • Heit JA, Armasu SM, Asmann YW, et al. A genome-wide association study of venous thromboembolism identifies risk variants in chromosomes 1q24.2 and 9q. J Thromb Haemost. 2012;10:1521–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Helgadottir A, Gretarsdottir S, Thorleifsson G, et al. Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism. J Am Coll Cardiol. 2012;60:722–9.

    CAS  PubMed  Google Scholar 

  • Hoffman M. Alterations of fibrinogen structure in human disease. Cardiovasc Hematol Agents Med Chem. 2008;6:206–11.

    CAS  PubMed  Google Scholar 

  • Hughes SD, Lou XJ, Ighani S, et al. Lipoprotein(a) vascular accumulation in mice. In vivo analysis of the role of lysine binding sites using recombinant adenovirus. J Clin Invest. 1997;100:1493–500.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Investigators R-C, Gordon AC, Mouncey PR, et al. Interleukin-6 receptor antagonists in critically ill patients with covid-19. N Engl J Med. 2021;384:1491–502.

    Google Scholar 

  • Ishikawa S, Kotani K, Kario K, et al. Inverse association between serum lipoprotein(a) and cerebral hemorrhage in the Japanese population. Thromb Res. 2013;131:e54–8.

    CAS  PubMed  Google Scholar 

  • Jaeger BR, Richter Y, Nagel D, et al. Longitudinal cohort study on the effectiveness of lipid apheresis treatment to reduce high lipoprotein(a) levels and prevent major adverse coronary events. Nat Clin Pract Cardiovasc Med. 2009;6:229–39.

    CAS  PubMed  Google Scholar 

  • Kagawa A, Azuma H, Akaike M, Kanagawa Y, Matsumoto T. Aspirin reduces apolipoprotein(a) (apo(a)) production in human hepatocytes by suppression of apo(a) gene transcription. J Biol Chem. 1999;274:34111–5.

    CAS  PubMed  Google Scholar 

  • Kamstrup PR, Benn M, Tybjaerg-Hansen A, Nordestgaard BG. Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: the Copenhagen City Heart Study. Circulation. 2008;117:176–84.

    CAS  PubMed  Google Scholar 

  • Kamstrup PR, Tybjaerg-Hansen A, Nordestgaard BG. Genetic evidence that lipoprotein(a) associates with atherosclerotic stenosis rather than venous thrombosis. Arterioscler Thromb Vasc Biol. 2012;32:1732–41.

    CAS  PubMed  Google Scholar 

  • Kenet G, Lutkhoff LK, Albisetti M, et al. Impact of thrombophilia on risk of arterial ischemic stroke or cerebral sinovenous thrombosis in neonates and children: a systematic review and meta-analysis of observational studies. Circulation. 2010;121:1838–47.

    PubMed  Google Scholar 

  • Khera AV, Everett BM, Caulfield MP, et al. Lipoprotein(a) concentrations, rosuvastatin therapy, and residual vascular risk: an analysis from the JUPITER Trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin). Circulation. 2014;129:635–42.

    CAS  PubMed  Google Scholar 

  • Kim JW, Seo HS, Suh SY, et al. Relationship between lipoprotein(a) and spontaneous recanalization of infarct-related arteries in the early phase of acute myocardial infarction. Clin Cardiol. 2008;31:211–6.

    PubMed  PubMed Central  Google Scholar 

  • Klezovitch O, Edelstein C, Zhu L, Scanu AM. Apolipoprotein(a) binds via its C-terminal domain to the protein core of the proteoglycan decorin. Implications for the retention of lipoprotein(a) in atherosclerotic lesions. J Biol Chem. 1998;273:23856–65.

    CAS  PubMed  Google Scholar 

  • Kostner GM, Bihari-Varga M. Is the atherogenicity of Lp(a) caused by its reactivity with proteoglycans? Eur Heart J. 1990;11(Suppl E):184–9.

    CAS  PubMed  Google Scholar 

  • Kronenberg F, Utermann G. Lipoprotein(a): resurrected by genetics. J Intern Med. 2013;273:6–30.

    CAS  PubMed  Google Scholar 

  • Kyriakou T, Seedorf U, Goel A, et al. A common LPA null allele associates with lower lipoprotein(a) levels and coronary artery disease risk. Arterioscler Thromb Vasc Biol. 2014;34:2095–9.

    CAS  PubMed  Google Scholar 

  • Lados-Krupa A, Konieczynska M, Chmiel A, Undas A. Increased oxidation as an additional mechanism underlying reduced clot permeability and impaired fibrinolysis in type 2 diabetes. J Diabetes Res. 2015;2015:456189.

    PubMed  PubMed Central  Google Scholar 

  • Lanktree MB, Anand SS, Yusuf S, Hegele RA, Investigators S. Comprehensive analysis of genomic variation in the LPA locus and its relationship to plasma lipoprotein(a) in South Asians, Chinese, and European Caucasians. Circ Cardiovasc Genet. 2010;3:39–46.

    CAS  PubMed  Google Scholar 

  • Larsson SC, Gill D, Mason AM, et al. Lipoprotein(a) in Alzheimer, Atherosclerotic, Cerebrovascular, Thrombotic, and Valvular Disease: Mendelian Randomization Investigation. Circulation. 2020;141:1826–8.

    PubMed  Google Scholar 

  • Lawn RM, Boonmark NW, Schwartz K, et al. The recurring evolution of lipoprotein(a). Insights from cloning of hedgehog apolipoprotein(a). J Biol Chem. 1995;270:24004–9.

    CAS  PubMed  Google Scholar 

  • Leebmann J, Roeseler E, Julius U, et al. Lipoprotein apheresis in patients with maximally tolerated lipid-lowering therapy, lipoprotein(a)-hyperlipoproteinemia, and progressive cardiovascular disease: prospective observational multicenter study. Circulation. 2013;128:2567–76.

    CAS  PubMed  Google Scholar 

  • Levin EG, Miles LA, Fless GM, et al. Lipoproteins inhibit the secretion of tissue plasminogen activator from human endothelial cells. Arterioscler Thromb. 1994;14:438–42.

    CAS  PubMed  Google Scholar 

  • Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011;473:317–25.

    CAS  PubMed  Google Scholar 

  • Lippi G, Guidi G. Lipoprotein(a): from ancestral benefit to modern pathogen? QJM. 2000;93:75–84.

    CAS  PubMed  Google Scholar 

  • Lippi G, Giampaolo L, Guidi G. Effects of anticoagulants on lipoprotein(a) measurements with four commercial assays. Eur J Clin Chem Clin Biochem. 1996;34:251–5.

    CAS  PubMed  Google Scholar 

  • Loscalzo J, Weinfeld M, Fless GM, Scanu AM. Lipoprotein(a), fibrin binding, and plasminogen activation. Arteriosclerosis. 1990;10:240–5.

    CAS  PubMed  Google Scholar 

  • Ma GS, Wilkinson MJ, Reeves RR, et al. Lipoprotein(a) in patients undergoing transcatheter aortic valve replacement. Angiology. 2019;70:332–6.

    CAS  PubMed  Google Scholar 

  • McLean JW, Tomlinson JE, Kuang WJ, et al. cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature. 1987;330:132–7.

    CAS  PubMed  Google Scholar 

  • Miller PE, Martin SS, Toth PP, et al. Screening and advanced lipid phenotyping in familial hypercholesterolemia: The Very Large Database of Lipids Study-17 (VLDL-17). J Clin Lipidol. 2015;9:676–83.

    PubMed  Google Scholar 

  • Moeslinger T, Friedl R, Spieckermann PG. Inhibition of inducible nitric oxide synthesis by azathioprine in a macrophage cell line. Life Sci. 2006;79:374–81.

    CAS  PubMed  Google Scholar 

  • Moliterno DJ, Lange RA, Meidell RS, et al. Relation of plasma lipoprotein(a) to infarct artery patency in survivors of myocardial infarction. Circulation. 1993;88:935–40.

    CAS  PubMed  Google Scholar 

  • Moreau M, Brocheriou I, Petit L, Ninio E, Chapman MJ, Rouis M. Interleukin-8 mediates downregulation of tissue inhibitor of metalloproteinase-1 expression in cholesterol-loaded human macrophages: relevance to stability of atherosclerotic plaque. Circulation. 1999;99:420–6. PMID: 30934954. Matrix Metalloproteinase 9 as a Predictor of Coronary Atherosclerotic Plaque Instability in Stable Coronary Heart Disease Patients with Elevated Lipoprotein(a) Levels.

    Google Scholar 

  • Moriarty PM. Lipoprotein apheresis: present and future uses. Curr Opin Lipidol. 2015;26:544–52.

    CAS  PubMed  Google Scholar 

  • Moriarty PM, Tennant H, Sehar N, et al. Case report of male child with elevated lipoprotein (a) leading to acute ischemic stroke. J Clin Apher. 2017;32:574–8.

    PubMed  Google Scholar 

  • Nguyen S, Ilano L, Oluoha N, Pakbaz Z. Lipoprotein(a) a risk factor for venous thrombosis and pulmonary embolism in patients younger than 50 years of age. Blood. 2018;132:5055.

    Google Scholar 

  • Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31:2844–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nowak-Gottl U, Debus O, Findeisen M, et al. Lipoprotein (a): its role in childhood thromboembolism. Pediatrics. 1997;99:E11.

    CAS  PubMed  Google Scholar 

  • Nugent AK, Gray JV, Gorby LK, Moriarty PM. Lipoprotein apheresis: first FDA indicated treatment for elevated lipoprotein(a). J Clin Cardiol. 2020;1:16–21.

    Google Scholar 

  • O’Donoghue ML, Morrow DA, Tsimikas S, et al. Lipoprotein(a) for risk assessment in patients with established coronary artery disease. J Am Coll Cardiol. 2014;63:520–7.

    PubMed  Google Scholar 

  • O’Donoghue ML, Fazio S, Giugliano RP, et al. Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk. Circulation. 2019;139:1483–92.

    PubMed  Google Scholar 

  • Paciullo F, Giannandrea D, Virgili G, Cagini C, Gresele P. Role of increased lipoprotein (a) in retinal vein occlusion: a systematic review and meta-analysis. TH Open. 2021;5:e295–302.

    PubMed  PubMed Central  Google Scholar 

  • Palabrica TM, Liu AC, Aronovitz MJ, Furie B, Lawn RM, Furie BC. Antifibrinolytic activity of apolipoprotein(a) in vivo: human apolipoprotein(a) transgenic mice are resistant to tissue plasminogen activator-mediated thrombolysis. Nat Med. 1995;1:256–9.

    CAS  PubMed  Google Scholar 

  • Pellegrino M, Furmaniak-Kazmierczak E, LeBlanc JC, et al. The apolipoprotein(a) component of lipoprotein(a) stimulates actin stress fiber formation and loss of cell-cell contact in cultured endothelial cells. J Biol Chem. 2004;279:6526–33.

    CAS  PubMed  Google Scholar 

  • Perombelon YF, Soutar AK, Knight BL. Variation in lipoprotein(a) concentration associated with different apolipoprotein(a) alleles. J Clin Invest. 1994;93:1481–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pierini FS, Botta E, Soriano ER, et al. Effect of tocilizumab on LDL and HDL characteristics in patients with rheumatoid arthritis. An observational study. Rheumatol Ther. 2021;8:803–15.

    PubMed  PubMed Central  Google Scholar 

  • Rand ML, Sangrar W, Hancock MA, et al. Apolipoprotein(a) enhances platelet responses to the thrombin receptor-activating peptide SFLLRN. Arterioscler Thromb Vasc Biol. 1998;18:1393–9.

    CAS  PubMed  Google Scholar 

  • Ranga GS, Kalra OP, Tandon H, Gambhir JK, Mehrotra G. Effect of aspirin on lipoprotein(a) in patients with ischemic stroke. J Stroke Cerebrovasc Dis. 2007;16:220–4.

    PubMed  Google Scholar 

  • Reyes-Soffer G, Ginsberg HN, Berglund L, et al. Lipoprotein(a): a genetically determined, causal, and prevalent risk factor for atherosclerotic cardiovascular disease: a scientific statement from the American Heart Association. Arterioscler Thromb Vasc Biol. 2022;42(1):e48–e60.

    Google Scholar 

  • Rodger MA, Le Gal G, Carrier M, et al. Serum lipoprotein (a) levels in patients with first unprovoked venous thromboembolism is not associated with subsequent risk of recurrent VTE. Thromb Res. 2010;126:222–6.

    CAS  PubMed  Google Scholar 

  • Romagnuolo R, Marcovina SM, Boffa MB, Koschinsky ML. Inhibition of plasminogen activation by apo(a): role of carboxyl-terminal lysines and identification of inhibitory domains in apo(a). J Lipid Res. 2014;55:625–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Safarova MS, Ezhov MV, Afanasieva OI, et al. Effect of specific lipoprotein(a) apheresis on coronary atherosclerosis regression assessed by quantitative coronary angiography. Atheroscler Suppl. 2013;14:93–9.

    CAS  PubMed  Google Scholar 

  • Said MA, Yeung MW, van de Vegte YJ, et al. Genome-wide association study and identification of a protective missense variant on lipoprotein(a) concentration: protective missense variant on lipoprotein(a) concentration-brief report. Arterioscler Thromb Vasc Biol. 2021;41:1792–800.

    CAS  PubMed  Google Scholar 

  • Satterfield BA, Dikilitas O, Safarova MS, et al. Associations of genetically predicted lipoprotein (a) levels with cardiovascular traits in individuals of European and African Ancestry. Circ Genom Precis Med. 2021;14(4):e003354.

    Google Scholar 

  • Scipione CA, McAiney JT, Simard DJ, et al. Characterization of the I4399M variant of apolipoprotein(a): implications for altered prothrombotic properties of lipoprotein(a). J Thromb Haemost. 2017;15:1834–44.

    CAS  PubMed  Google Scholar 

  • Simon DI, Fless GM, Scanu AM, Loscalzo J. Tissue-type plasminogen activator binds to and is inhibited by surface-bound lipoprotein(a) and low-density lipoprotein. Biochemistry. 1991;30:6671–7.

    CAS  PubMed  Google Scholar 

  • Skuza AA, Polak M, Undas A. Elevated lipoprotein(a) as a new risk factor of cerebral venous sinus thrombosis: association with fibrin clot properties. J Thromb Thrombolysis. 2019;47:8–15.

    CAS  PubMed  Google Scholar 

  • Sofi F, Marcucci R, Abbate R, Gensini GF, Prisco D. Lipoprotein (a) and venous thromboembolism in adults: a meta-analysis. Am J Med. 2007;120:728–33.

    CAS  PubMed  Google Scholar 

  • Stefanutti C, Mazza F, Pasqualetti D, et al. Lipoprotein apheresis downregulates IL-1 alpha, IL-6 and TNF-alpha mRNA expression in severe dyslipidaemia. Atheroscler Suppl. 2017;30:200–8.

    PubMed  Google Scholar 

  • Sticchi E, Magi A, Kamstrup PR, et al. Apolipoprotein(a) kringle-IV type 2 copy number variation is associated with venous thromboembolism. PLoS One. 2016;11:e0149427.

    PubMed  PubMed Central  Google Scholar 

  • Stiekema LCA, Stroes ESG, Verweij SL, et al. Persistent arterial wall inflammation in patients with elevated lipoprotein(a) despite strong low-density lipoprotein cholesterol reduction by proprotein convertase subtilisin/kexin type 9 antibody treatment. Eur Heart J. 2019;40:2775–81.

    CAS  PubMed  Google Scholar 

  • Strang AC, Bisoendial RJ, Kootte RS, et al. Pro-atherogenic lipid changes and decreased hepatic LDL receptor expression by tocilizumab in rheumatoid arthritis. Atherosclerosis. 2013;229:174–81.

    CAS  PubMed  Google Scholar 

  • Tabas I, Li Y, Brocia RW, Xu SW, Swenson TL, Williams KJ. Lipoprotein lipase and sphingomyelinase synergistically enhance the association of atherogenic lipoproteins with smooth muscle cells and extracellular matrix. A possible mechanism for low density lipoprotein and lipoprotein(a) retention and macrophage foam cell formation. J Biol Chem. 1993;268:20419–32.

    CAS  PubMed  Google Scholar 

  • Takami S, Yamashita S, Kihara S, et al. Lipoprotein(a) enhances the expression of intercellular adhesion molecule-1 in cultured human umbilical vein endothelial cells. Circulation. 1998;97:721–8.

    CAS  PubMed  Google Scholar 

  • Tsimikas S. A test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol. 2017;69:692–711.

    CAS  PubMed  Google Scholar 

  • Tsimikas S, Fazio S, Ferdinand KC, et al. NHLBI Working Group recommendations to reduce lipoprotein(a)-mediated risk of cardiovascular disease and aortic stenosis. J Am Coll Cardiol. 2018;71:177–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tsironis LD, Mitsios JV, Milionis HJ, Elisaf M, Tselepis AD. Effect of lipoprotein (a) on platelet activation induced by platelet-activating factor: role of apolipoprotein (a) and endogenous PAF-acetylhydrolase. Cardiovasc Res. 2004;63:130–8.

    CAS  PubMed  Google Scholar 

  • Tsurumi Y, Nagashima H, Ichikawa K, Sumiyoshi T, Hosoda S. Influence of plasma lipoprotein (a) levels on coronary vasomotor response to acetylcholine. J Am Coll Cardiol. 1995;26:1242–50.

    CAS  PubMed  Google Scholar 

  • Undas A, Stepien E, Tracz W, Szczeklik A. Lipoprotein(a) as a modifier of fibrin clot permeability and susceptibility to lysis. J Thromb Haemost. 2006;4:973–5.

    CAS  PubMed  Google Scholar 

  • van der Valk FM, Bekkering S, Kroon J, et al. Oxidized phospholipids on lipoprotein(a) elicit arterial wall inflammation and an inflammatory monocyte response in humans. Circulation. 2016;134:611–24.

    PubMed  PubMed Central  Google Scholar 

  • van Wijk DF, Sjouke B, Figueroa A, et al. Nonpharmacological lipoprotein apheresis reduces arterial inflammation in familial hypercholesterolemia. J Am Coll Cardiol. 2014;64:1418–26.

    PubMed  Google Scholar 

  • von Depka M, Nowak-Gottl U, Eisert R, et al. Increased lipoprotein (a) levels as an independent risk factor for venous thromboembolism. Blood. 2000;96:3364–8.

    Google Scholar 

  • von Zychlinski A, Kleffmann T, Williams MJ, McCormick SP. Proteomics of Lipoprotein(a) identifies a protein complement associated with response to wounding. J Proteome. 2011;74:2881–91.

    Google Scholar 

  • Wade DP, Clarke JG, Lindahl GE, et al. 5′ control regions of the apolipoprotein(a) gene and members of the related plasminogen gene family. Proc Natl Acad Sci U S A. 1993;90:1369–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Willeit P, Ridker PM, Nestel PJ, et al. Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials. Lancet. 2018;392:1311–20.

    CAS  PubMed  Google Scholar 

  • Zimman A, Mouillesseaux KP, Le T, et al. Vascular endothelial growth factor receptor 2 plays a role in the activation of aortic endothelial cells by oxidized phospholipids. Arterioscler Thromb Vasc Biol. 2007;27:332–8.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Atherosclerosis and Lipid Genomics Laboratory, Mayo Clinic, Rochester, MN, USA

    Maya S. Safarova

  2. Department of Cardiovascular Medicine, University of Kansas Hospital and Medical Center, Kansas City, KS, USA

    Maya S. Safarova

  3. Division of Endocrinology, Diabetes and Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA

    Patrick M. Moriarty

  4. Atherosclerosis and Lipoprotein Apheresis Center, University of Kansas Medical Center, Kansas City, KS, USA

    Patrick M. Moriarty

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Correspondence to Patrick M. Moriarty .

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  1. Mater Hospital, University of Queensland, Brisbane, QLD, Australia

    Karam Kostner

  2. Medical University of Graz, Graz, Austria

    Gerhard M. Kostner

  3. Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Peter P. Toth

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Safarova, M.S., Moriarty, P.M. (2023). Thrombosis, Inflammation, and Lipoprotein(a): Clinical Implications. In: Kostner, K., Kostner, G.M., Toth, P.P. (eds) Lipoprotein(a). Contemporary Cardiology. Humana, Cham. https://doi.org/10.1007/978-3-031-24575-6_11

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  • DOI: https://doi.org/10.1007/978-3-031-24575-6_11

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  • Publisher Name: Humana, Cham

  • Print ISBN: 978-3-031-24574-9

  • Online ISBN: 978-3-031-24575-6

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