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Updated: Mar 20, 2026

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
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PCSK9 Inhibitors.

Pradeep Natarajan1, Sekar Kathiresan1

  • 1Center for Human Genetic Research and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA.

Cell
|May 21, 2016
PubMed
Summary
This summary is machine-generated.

Alirocumab and evolocumab are monoclonal antibodies that inhibit PCSK9, increasing LDL receptors and lowering LDL cholesterol. These therapies effectively reduce LDL cholesterol, a key factor in atherosclerotic cardiovascular disease.

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Area of Science:

  • Cardiovascular Medicine
  • Pharmacology

Background:

  • Atherosclerotic cardiovascular disease (ASCVD) is a major health concern.
  • Elevated low-density lipoprotein (LDL) cholesterol is a primary driver of ASCVD.
  • Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in regulating LDL receptors.

Purpose of the Study:

  • To review the mechanisms and efficacy of PCSK9 inhibitors.
  • To highlight the role of alirocumab and evolocumab in managing hypercholesterolemia.

Main Methods:

  • Review of preclinical and clinical studies on alirocumab and evolocumab.
  • Analysis of PCSK9 inhibition's effect on LDL receptor expression and plasma LDL cholesterol levels.

Main Results:

  • Alirocumab and evolocumab effectively block PCSK9.
  • These therapies lead to increased LDL receptor availability on cell surfaces.
  • Significant reductions in plasma LDL cholesterol are observed with both agents.

Conclusions:

  • PCSK9 inhibitors represent a significant advancement in lipid-lowering therapy.
  • Alirocumab and evolocumab offer effective treatment options for patients with hypercholesterolemia and ASCVD risk.