The atherogenic role of immune cells in familial hypercholesterolemia.

Eskandar Taghizadeh, Forough Taheri, Seyed Mohammad Gheibi Hayat, Fabrizio Montecucco, Federico Carbone, Daryoush Rostami, Ardalan Montazeri, Amirhossein Sahebkar

Journal: IUBMB life 2021;72(4):782-789

PMID: 31633867

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Abstract

Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lipoprotein metabolism that mainly occurs due to mutations in the low-density lipoprotein receptor gene and is characterized by increased levels of low-density lipoprotein cholesterol, leading to accelerated atherogenesis and premature coronary heart disease. Both innate and adaptive immune responses, which mainly include monocytes, macrophages, neutrophils, T lymphocytes, and B lymphocytes, have been shown to play a key role for the initiation and progression of atherogenesis in the general population. In FH patients, these immune cells have been suggested to play specific pro-atherosclerotic activities, from the initial leukocyte recruitment to plaque rupture. In fact, the accumulation of cholesterol crystals and oxLDL in the vessels in FH patients is particularly high, with consequent abnormal mobilization of immune cells and secretion of various pro-inflammatory and chemokines. In addition, cholesterol accumulation in immune cells is exaggerated with chronic exposure to relevant pro-atherosclerotic triggers. The topics considered in this review may provide a more specific focus on the immune system alterations in FH and open new insights toward immune cells as potential therapeutic targets in FH.

Address: Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.; Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.; Shahrekord Branch, Islamic Azad University, Iran.; Department of Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.; First Clinic of Internal Medicine, Department of Internal Medicine, and Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy.; First Clinic of Internal Medicine, IRCCS Ospedale Policlinico San Martino Genoa-Italian Cardiovascular Network, Genoa, Italy.; First Clinic of Internal Medicine, IRCCS Ospedale Policlinico San Martino Genoa-Italian Cardiovascular Network, Genoa, Italy.; First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.; Department of School Allied, Zabol University of Medical Sciences, Zabol, Iran.; Department of Biology, Faculty of Science, Central Tehran Branch, Islamic Azad University, Tehran, Iran.; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

DOI: 10.1002/iub.2179

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https://assays.cancer.gov/non-CPTAC-3579

MeSH Terms: Atherosclerosis, B-Lymphocytes, Humans, Hyperlipoproteinemia Type II, Macrophages, Neutrophils, T-Lymphocytes