Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease?

Elevated plasma concentrations of lipoprotein (a) [Lp(a)] have been determined to be a causal risk factor for coronary heart disease, and may similarly play a role in other atherothrombotic disorders. Lp(a) consists of a lipoprotein moiety indistinguishable from LDL, as well as the plasminogen-relat...

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Main Authors: Michael B. Boffa, Marlys L. Koschinsky
Format: Article
Language:English
Published: Elsevier 2016-05-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520309792
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author Michael B. Boffa
Marlys L. Koschinsky
author_facet Michael B. Boffa
Marlys L. Koschinsky
author_sort Michael B. Boffa
collection DOAJ
description Elevated plasma concentrations of lipoprotein (a) [Lp(a)] have been determined to be a causal risk factor for coronary heart disease, and may similarly play a role in other atherothrombotic disorders. Lp(a) consists of a lipoprotein moiety indistinguishable from LDL, as well as the plasminogen-related glycoprotein, apo(a). Therefore, the pathogenic role for Lp(a) has traditionally been considered to reflect a dual function of its similarity to LDL, causing atherosclerosis, and its similarity to plasminogen, causing thrombosis through inhibition of fibrinolysis. This postulate remains highly speculative, however, because it has been difficult to separate the prothrombotic/antifibrinolytic functions of Lp(a) from its proatherosclerotic functions. This review surveys the current landscape surrounding these issues: the biochemical basis for procoagulant and antifibrinolytic effects of Lp(a) is summarized and the evidence addressing the role of Lp(a) in both arterial and venous thrombosis is discussed. While elevated Lp(a) appears to be primarily predisposing to thrombotic events in the arterial tree, the fact that most of these are precipitated by underlying atherosclerosis continues to confound our understanding of the true pathogenic roles of Lp(a) and, therefore, the most appropriate therapeutic target through which to mitigate the harmful effects of this lipoprotein.
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spelling doaj.art-7d2552feb074407b85b8bb86ec586bf32022-12-21T21:31:04ZengElsevierJournal of Lipid Research0022-22752016-05-01575745757Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease?Michael B. Boffa0Marlys L. Koschinsky1Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON, CanadaTo whom correspondence should be addressed; Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON, Canada; Robarts Research Institute, Western University, London, ON, CanadaElevated plasma concentrations of lipoprotein (a) [Lp(a)] have been determined to be a causal risk factor for coronary heart disease, and may similarly play a role in other atherothrombotic disorders. Lp(a) consists of a lipoprotein moiety indistinguishable from LDL, as well as the plasminogen-related glycoprotein, apo(a). Therefore, the pathogenic role for Lp(a) has traditionally been considered to reflect a dual function of its similarity to LDL, causing atherosclerosis, and its similarity to plasminogen, causing thrombosis through inhibition of fibrinolysis. This postulate remains highly speculative, however, because it has been difficult to separate the prothrombotic/antifibrinolytic functions of Lp(a) from its proatherosclerotic functions. This review surveys the current landscape surrounding these issues: the biochemical basis for procoagulant and antifibrinolytic effects of Lp(a) is summarized and the evidence addressing the role of Lp(a) in both arterial and venous thrombosis is discussed. While elevated Lp(a) appears to be primarily predisposing to thrombotic events in the arterial tree, the fact that most of these are precipitated by underlying atherosclerosis continues to confound our understanding of the true pathogenic roles of Lp(a) and, therefore, the most appropriate therapeutic target through which to mitigate the harmful effects of this lipoprotein.http://www.sciencedirect.com/science/article/pii/S0022227520309792apolipoproteinsatherosclerosislow density lipoproteinlipoproteinslipoproteins/kineticsapolipoprotein (a)
spellingShingle Michael B. Boffa
Marlys L. Koschinsky
Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease?
Journal of Lipid Research
apolipoproteins
atherosclerosis
low density lipoprotein
lipoproteins
lipoproteins/kinetics
apolipoprotein (a)
title Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease?
title_full Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease?
title_fullStr Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease?
title_full_unstemmed Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease?
title_short Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease?
title_sort lipoprotein a truly a direct prothrombotic factor in cardiovascular disease
topic apolipoproteins
atherosclerosis
low density lipoprotein
lipoproteins
lipoproteins/kinetics
apolipoprotein (a)
url http://www.sciencedirect.com/science/article/pii/S0022227520309792
work_keys_str_mv AT michaelbboffa lipoproteinatrulyadirectprothromboticfactorincardiovasculardisease
AT marlyslkoschinsky lipoproteinatrulyadirectprothromboticfactorincardiovasculardisease