Ajoolabady, A, Pratico, D, Mazidi, M, Davies, IG, Lip, GYH, Seidah, N, Libby, P, Kroemer, G and Ren, J (2024) PCSK9 in metabolism and diseases. Metabolism, 163. pp. 1-26. ISSN 0026-0495

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Abstract

PCSK9 is a serine protease that regulates plasma levels of low-density lipoprotein (LDL) and cholesterol by mediating the endolysosomal degradation of LDL receptor (LDLR) in the liver. When PCSK9 functions unchecked, it leads to increased degradation of LDLR, resulting in elevated circulatory levels of LDL and cholesterol. This dysregulation contributes to lipid and cholesterol metabolism abnormalities, foam cell formation, and the development of various diseases, including cardiovascular disease (CVD), viral infections, cancer, and sepsis. Emerging clinical and experimental evidence highlights an imperative role for PCSK9 in metabolic anomalies such as hypercholesterolemia and hyperlipidemia, as well as inflammation, and disturbances in mitochondrial homeostasis. Moreover, metabolic hormones - including insulin, glucagon, adipokines, natriuretic peptides, and sex steroids - regulate the expression and circulatory levels of PCSK9, thus influencing cardiovascular and metabolic functions. In this comprehensive review, we aim to elucidate the regulatory role of PCSK9 in lipid and cholesterol metabolism, pathophysiology of diseases such as CVD, infections, cancer, and sepsis, as well as its pharmaceutical and non-pharmaceutical targeting for therapeutic management of these conditions.

Item Type:	Article
Uncontrolled Keywords:	Atherosclerosis; Cardiovascular disease (CVD); Clinical trials; Inflammation; Lipid and cholesterol metabolism; Metabolic hormones; PCSK9; Health Disparities; Sepsis; Minority Health; Cardiovascular; Atherosclerosis; Infectious Diseases; Heart Disease; Nutrition; Liver Disease; Hematology; Digestive Diseases; 2.1 Biological and endogenous factors; 1.1 Normal biological development and functioning; 3 Good Health and Well Being; 1103 Clinical Sciences; Endocrinology & Metabolism
Subjects:	R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions:	Nursing and Advanced Practice Sport and Exercise Sciences
Publisher:	Elsevier BV
SWORD Depositor:	A Symplectic
Date Deposited:	14 Jan 2025 09:33
Last Modified:	14 Jan 2025 09:33
DOI or ID number:	10.1016/j.metabol.2024.156064
URI:	https://researchonline.ljmu.ac.uk/id/eprint/25098

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