Hypercholesterolemia: The role of PCSK9

• Published in: Archives of biochemistry and biophysics 2017-07, Vol.625-626, p.39-53
• Main Authors: Melendez, Quantil M., Krishnaji, Sreevidhya T., Wooten, Catherine J., Lopez, Dayami
• Format: Article
• Language: English
• Subjects: Animals; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypercholesterolemia; Hypercholesterolemia - drug therapy; Hypercholesterolemia - genetics; Hypercholesterolemia - metabolism; Hypercholesterolemia - pathology; IDOL; Inhibitors; LDL; LDL receptor; Metabolic diseases; PCSK9; Plaque, Atherosclerotic - drug therapy; Plaque, Atherosclerotic - genetics; Plaque, Atherosclerotic - metabolism; Plaque, Atherosclerotic - pathology; Proprotein Convertase 9 - analysis; Proprotein Convertase 9 - metabolism; Receptors, LDL - genetics; Receptors, LDL - metabolism; Statin; Ubiquitin-Protein Ligases - metabolism
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2017.06.001

Heart disease ends the life of more people than any other disease in the United States. High levels of low density lipoprotein (LDL)-cholesterol cause heart diseases by increasing the formation of atherosclerotic plaques. Proprotein convertase subtilisin/kexin-9 (PCSK9) indirectly regulates plasma LDL levels by controlling the LDL receptor expression at the plasma membrane. PCSK9 also appears to modulate glucose intolerance, insulin resistance, abdominal obesity, inflammation, and hypertension. The magnitude of PCSK9's involvement in the onset of these metabolic abnormalities appears to be associated with age, sex, and ethnic background. Another regulator, the inducible degrader of the LDL receptor (IDOL), works by enhancing the ubiquitination of the LDL receptor. Herein, we will review the functions and regulatory mechanisms of PCSK9. The effects of PCSK9 on the LDL receptor, the relationship of this convertase with IDOL, and treatments currently available against hypercholesterolemia are also discussed. •The LDL receptor, its regulators, and current lipid lowering drugs are discussed.•PCSK9 controls serum LDL levels and the onset of multiple metabolic diseases.•PCSK9's role in disease onset is dependent on age, sex, and ethnic background.•IDOL works mainly by reducing the LDL receptor leading to high LDL levels.•More personalized treatment options are still needed to address all patients.