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Molecular Mechanisms of Lipoprotein(a) Pathogenicity: Tantalizing Clues and Unanswered Questions

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Lipoprotein(a)

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

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Abstract

Although elevated levels of lipoprotein(a) (Lp(a)) are increasingly recognized as a causal risk factor for the development of premature cardiovascular disease, the precise mechanisms by which Lp(a) exerts its harmful effects remain unclear. Studies using in vitro cell model systems—and a few in vivo studies in humans and animal models—show that Lp(a) and its unique constituent lipoprotein(a) (apo(a)) elicit pathological changes in vascular endothelial cells and smooth muscle cells, in circulating monocytes, and in macrophages. These effects together could promote the initiation and progression of atherosclerosis and favor the development of vulnerable plaques. Many of these changes are specifically mediated by the oxidized phospholipid that is covalently associated with kringle IV type 10 in apo(a). While in vitro and in vivo data are conflicting regarding a direct role of Lp(a) in inhibiting fibrinolysis, further studies are required to fully elaborate the role of Lp(a) in triggering thrombosis versus the development of thrombosis-prone atherosclerotic plaques. Lp(a) and apo(a) can also promote calcific aortic valve disease by promoting pro-osteogenic and proinflammatory responses in valve interstitial cells; again, the oxidized phospholipid in apo(a) plays a central role in this process.

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Authors and Affiliations

  1. Robarts Research Institute, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada

    Michael B. Boffa & Marlys L. Koschinsky

  2. Department of Biochemistry, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada

    Michael B. Boffa

  3. Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada

    Marlys L. Koschinsky

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Correspondence to Michael B. Boffa .

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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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Boffa, M.B., Koschinsky, M.L. (2023). Molecular Mechanisms of Lipoprotein(a) Pathogenicity: Tantalizing Clues and Unanswered Questions. 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_10

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