Hypercholesterolemia: The role of PCSK9

Quantil M Melendez; Sreevidhya T Krishnaji; Catherine J Wooten; Dayami Lopez

doi:10.1016/j.abb.2017.06.001

Hypercholesterolemia: The role of PCSK9

Arch Biochem Biophys. 2017 Jul 1:625-626:39-53. doi: 10.1016/j.abb.2017.06.001. Epub 2017 Jun 3.

Authors

Quantil M Melendez¹, Sreevidhya T Krishnaji², Catherine J Wooten¹, Dayami Lopez³

Affiliations

¹ Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise (BRITE), College of Arts and Sciences, North Carolina Central University, Durham, NC 27707, USA.
² Indian Institute of Science Education and Research, Bhopal, Madhya Pradesh, India.
³ Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise (BRITE), College of Arts and Sciences, North Carolina Central University, Durham, NC 27707, USA. Electronic address: lopezd@nccu.edu.

PMID: 28587771
DOI: 10.1016/j.abb.2017.06.001

Abstract

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.

Keywords: Hypercholesterolemia; IDOL; Inhibitors; LDL; LDL receptor; Metabolic diseases; PCSK9; Statin.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
Hypercholesterolemia / drug therapy
Hypercholesterolemia / genetics
Hypercholesterolemia / metabolism*
Hypercholesterolemia / pathology
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*
Ubiquitin-Protein Ligases / metabolism

Substances

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Receptors, LDL
MYLIP protein, human
Ubiquitin-Protein Ligases
PCSK9 protein, human
Proprotein Convertase 9