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Macrophage Cholesterol Efflux and Atherosclerosis in Psoriasis: A role for microRNA‐33
Author(s) -
Karunakaran Denuja,
Dwevidi Girish,
Rayner Katey
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.947.7
Subject(s) - macrophage , inflammation , abca1 , efflux , psoriasis , cholesterol , reverse cholesterol transport , medicine , immunology , endocrinology , chemistry , lipoprotein , transporter , biochemistry , gene , in vitro
Psoriatic patients have an increased risk in developing atherosclerosis. However, the precise mechanism by which the localized skin inflammation drives atherosclerosis is unclear. Macrophages have been shown to promote localized skin inflammation and also drive atherosclerosis by retaining modified excess cholesterol. Macrophage cholesterol efflux depends on 2 elements: (i) functional circulating HDL interacting with (ii) macrophage ABCA1 cholesterol transporter to release the excess cholesterol into HDL particles to be cleared. microRNA‐33 (miR‐33) levels are markedly elevated in CAD and it directly targets various genes regulating cholesterol transport, mitochondrial function and inflammation to inhibit macrophage cholesterol efflux, promoting atherosclerosis. Thus, novel therapeutics aims to inhibit miR‐33 to treat atherosclerosis. Nonetheless, the mechanism by which macrophage miR‐33 drives atherosclerosis in psoriasis and how psoriasiform‐inflammation accelerates atherosclerosis remains to be elucidated. Here, we aim to determine if psoriasiform macrophages have elevated miR‐33 levels and are defective in mediating cholesterol efflux and thus, accelerating atherosclerosis. Preliminary data indicate that human macrophages treated with key cytokines (e.g. IL‐17A or IL‐23 or TNFα) that drive psoriatic inflammation have increased miR‐33a expression and decreased macrophage cholesterol efflux. Ongoing studies are investigating whether human primary macrophages derived from psoriatic patients have decreased cholesterol efflux relative to control. These studies will provide mechanistic insight as to how miR‐33 is regulated in psoriasiform inflammation and whether anti‐miR33 therapy or other novel therapeutic targeting the macrophage efflux pathways can be used to treat cardiovascular disease in psoriatic patients.