Dyslipidemia, and specifically elevated low-density lipoprotein (LDL) cholesterol, is one of the most important cardiovascular risk factors. Statins are considered first line therapy for the primary and secondary prevention of cardiovascular disease. However, statins may not be adequate treatment for elevated circulating LDL levels and are ineffective in certain familial hypercholesterolemias. The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9), a regulatory protein that affects LDL receptors, offers a new alternative for these patients. Moreover, gain-of-function PCSK9 mutations were discovered to be the root cause of familial autosomal dominant hypercholesterolemia. Inhibition of PSCK9 reduces plasma LDL levels, even in patients for whom statins are ineffective or not tolerated. Alirocumab and evolocumab, human monoclonal antibodies that inhibit PCSK9, have been approved to lower LDL levels. While there are drawbacks to these treatments, including adverse events, administration by subcutaneous injection, and high cost, these drugs are indicated for the treatment of atherosclerotic cardiovascular disease and familial hypercholesterolemia as adjunct to diet and maximally tolerated statin therapy. PCSK9 inhibitors may work synergistically with statins to lower LDL. Novel approaches to PCSK9 inhibition are currently in development with the aim of providing safe and effective treatment options to decrease cardiovascular event burden, ideally at lower cost and with oral bioavailability.
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June 2018
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Double immunofluorescence staining for mindin (red) and CD68 (green) in atherosclerotic plaques of HFD-treated APOE-/- mice. In Issue 11 of Clinical Science, Zhu et al. discuss mindin deficiency as a novel mediator in protecting against foam cell formation and atherosclerosis, through direct interaction with LXR-β; for details, see pages 1199–1213.
Review Article|
June 09 2018
PCSK9 in cholesterol metabolism: from bench to bedside
Allison B. Reiss;
1Department of Medicine and Winthrop Research Institute, NYU Winthrop Hospital, 101 Mineola Boulevard, Suite 4-004, Mineola, NY 11501, U.S.A.
Correspondence: Allison B. Reiss ([email protected])
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Neal Shah;
Neal Shah
1Department of Medicine and Winthrop Research Institute, NYU Winthrop Hospital, 101 Mineola Boulevard, Suite 4-004, Mineola, NY 11501, U.S.A.
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Dalia Muhieddine;
Dalia Muhieddine
1Department of Medicine and Winthrop Research Institute, NYU Winthrop Hospital, 101 Mineola Boulevard, Suite 4-004, Mineola, NY 11501, U.S.A.
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Juan Zhen;
Juan Zhen
1Department of Medicine and Winthrop Research Institute, NYU Winthrop Hospital, 101 Mineola Boulevard, Suite 4-004, Mineola, NY 11501, U.S.A.
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Jennifer Yudkevich;
Jennifer Yudkevich
1Department of Medicine and Winthrop Research Institute, NYU Winthrop Hospital, 101 Mineola Boulevard, Suite 4-004, Mineola, NY 11501, U.S.A.
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Lora J. Kasselman;
Lora J. Kasselman
1Department of Medicine and Winthrop Research Institute, NYU Winthrop Hospital, 101 Mineola Boulevard, Suite 4-004, Mineola, NY 11501, U.S.A.
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Joshua DeLeon
Joshua DeLeon
2Division of Cardiology, NYU Winthrop Hospital, 2nd floor, 212 Jericho Turnpike, Mineola, NY 11501, U.S.A.
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Publisher: Portland Press Ltd
Received:
March 12 2018
Revision Received:
May 11 2018
Accepted:
May 14 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (11): 1135–1153.
Article history
Received:
March 12 2018
Revision Received:
May 11 2018
Accepted:
May 14 2018
Citation
Allison B. Reiss, Neal Shah, Dalia Muhieddine, Juan Zhen, Jennifer Yudkevich, Lora J. Kasselman, Joshua DeLeon; PCSK9 in cholesterol metabolism: from bench to bedside. Clin Sci (Lond) 14 June 2018; 132 (11): 1135–1153. doi: https://doi.org/10.1042/CS20180190
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