title: High-density lipoprotein deficiency in genetically modified mice deeply affects skin morphology: A structural and ultrastructural study.
abstract: Cutaneous lipids, endogenously synthetized and transported by lipoproteins, play a pivotal role in maintaining skin barrier. An impairment of extracutaneous lipid trafficking leads to the development of xanthomas, mostly arising in hyperlipidemic patients, but also in subjects with high-density lipoprotein (HDL) deficiency. The aim of this work was to evaluate, in a genetically modified mouse model, lacking two protein components of HDL particles, apolipoprotein(apo)E and apoA-I, the effect of HDL deficiency on skin morphology. Control mice (C57BL/6), apoE deficient mice (EKO), apoA-I deficient mice (A-IKO) and apoA-I/apoE double knockout mice (A-IKO/EKO) were maintained on a low-fat/low-cholesterol diet up to 30 weeks of age. At sacrifice, skin biopsies were processed for light (LM) and transmission electron microscopy (TEM). Whereas the skin of EKO, A-IKO, and C57BL/6 mice was comparable, LM analysis in A-IKO/EKO mice showed an increase in dermal thickness and the presence of foam cells and T lymphocytes in reticular dermis. TEM analysis revealed the accumulation of cholesterol clefts in the papillary dermis and of cholesterol crystals within foam cells. In conclusion, A-IKO/EKO mice represent an experimental model for investigating the cutaneous phenotype of human HDL deficiency, thus mimicking a condition in which human xanthomatous lesions can develop.
authors.affiliation: Department of Biomedical Sciences for Health, Laboratory of Structural and Ultrastructural Morphology, Italy. Electronic address: francesca.arnaboldi1@unimi.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Arnaboldi
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Laboratory of Pharmacology of Dyslipidemias and Atherosclerosis, Università degli Studi di Milano, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Busnelli
authors.affiliation: Department of Biomedical Sciences for Health, Laboratory of Structural and Ultrastructural Morphology, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cornaghi
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Laboratory of Pharmacology of Dyslipidemias and Atherosclerosis, Università degli Studi di Milano, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Manzini
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Laboratory of Pharmacology of Dyslipidemias and Atherosclerosis, Università degli Studi di Milano, Milan, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Parolini
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Laboratory of Pharmacology of Dyslipidemias and Atherosclerosis, Università degli Studi di Milano, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Dellera
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Laboratory of Pharmacology of Dyslipidemias and Atherosclerosis, Università degli Studi di Milano, Milan, Italy.
authors.forename: Giulia Sara
authors.initials: GS
authors.lastname: Ganzetti
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Laboratory of Pharmacology of Dyslipidemias and Atherosclerosis, Università degli Studi di Milano, Milan, Italy.
authors.forename: Cesare Riccardo
authors.initials: CR
authors.lastname: Sirtori
authors.affiliation: Department of Biomedical Sciences for Health, Laboratory of Structural and Ultrastructural Morphology, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Donetti
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Laboratory of Pharmacology of Dyslipidemias and Atherosclerosis, Università degli Studi di Milano, Milan, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Chiesa
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D052456:Hypoalphalipoproteinemias / Q000473:pathology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012867:Skin / Q000473:pathology*; D014973:Xanthomatosis / Q000235:genetics / Q000473:pathology
chemical_list: D016632:Apolipoprotein A-I; D001057:Apolipoproteins E
keywords: Apolipoproteins; Cholesterol clefts; HDLs; Transmission electron microscopy