Abstract
The proprotein convertase subtilisin/kexin type 9 (PCSK9) acts via a canonical pathway to regulate circulating low-density lipoprotein-cholesterol (LDL-C) via degradation of the LDL receptor (LDLR) on the liver cell surface. Published research has shown that PCSK9 is involved in atherosclerosis via a variety of non-classical mechanisms that involve lysosomal, inflammatory, apoptotic, mitochondrial, and immune pathways. In this review paper, we summarized these additional mechanisms and described how anti-PCSK9 therapy exerts effects through these mechanisms. These additional pathways further illustrate the regulatory role of PCSK9 in atherosclerosis and offer an in-depth interpretation of how the PCSK9 inhibitor exerts effects on the treatment of atherosclerosis.
Keywords:
Atherosclerosis; Inflammation; LDL-C; Mitochondrial DNA; PCSK9.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antibodies, Monoclonal / therapeutic use
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Anticholesteremic Agents / therapeutic use
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Atherosclerosis / blood
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Atherosclerosis / drug therapy
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Atherosclerosis / enzymology*
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Atherosclerosis / pathology
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Cholesterol, LDL / blood*
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Diabetes Mellitus / blood
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Diabetes Mellitus / enzymology*
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Diabetes Mellitus / pathology
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Dyslipidemias / blood
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Dyslipidemias / drug therapy
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Dyslipidemias / enzymology*
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Dyslipidemias / pathology
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Endothelial Cells / enzymology
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Endothelial Cells / pathology
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Humans
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Inflammation / blood
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Inflammation / enzymology*
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Inflammation / pathology
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Macrophages / enzymology
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Macrophages / pathology
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PCSK9 Inhibitors
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Plaque, Atherosclerotic
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Proprotein Convertase 9 / metabolism*
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Serine Proteinase Inhibitors / therapeutic use
Substances
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Antibodies, Monoclonal
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Anticholesteremic Agents
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Cholesterol, LDL
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PCSK9 Inhibitors
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Serine Proteinase Inhibitors
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PCSK9 protein, human
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Proprotein Convertase 9