title: Pro-inflammatory monocyte-macrophage polarization imbalance in human hypercholesterolemia and atherosclerosis.
abstract: Monocyte-macrophages (MoMas) play a major role in atherosclerosis. In mice, hypercholesterolemia increases pro-inflammatory monocytes that promote plaque growth, but whether this is true also in humans in unknown. We herein analyzed monocyte subsets and MoMa phenotypes in familiar (FH, n = 22) and non-familiar (NFH, n = 20) hypercholesterolemic compared with normocholesterolemic (CTRL, n = 20) patients. We found that FH and NFH had higher circulating pro-inflammatory CD68(+)CCR2(+) M1 MoMas than CTRL, while anti-inflammatory CX3CR1(+)CD163(+)/CD206(+) M2 MoMas were reduced only in NFH. As a result, the M1/M2 polarization balance was increased in FH and, more markedly in NFH. M1 MoMas and the M1/M2 polarization ratio were directly correlated to pre-treatment LDL cholesterol levels and strongly associated with the presence of atherosclerotic plaques. In conclusion, we show for the first time that human hypercholesterolemia is associated with a pro-inflammatory imbalance of circulating monocytic cells, which can predispose to the development of atherosclerosis.
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy. Electronic address: gianpaolofadini@hotmail.com.
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Fadini
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Simoni
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Cappellari
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Vitturi
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Galasso
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy.
authors.forename: Saula
authors.initials: S
authors.lastname: Vigili de Kreutzenberg
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Previato
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
mesh_terms: D050197:Atherosclerosis / Q000097:blood*; D001853:Bone Marrow / Q000378:metabolism; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D005487:Foam Cells / Q000378:metabolism; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood*; D007249:Inflammation / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology*; D010641:Phenotype; D058226:Plaque, Atherosclerotic / Q000378:metabolism*; D012307:Risk Factors
chemical_list: D008077:Lipoproteins, LDL
keywords: Bone marrow; Foam cells; Inflammation; Plaque