Lehti , S , Nguyen , S D , Belevich , I , Vihinen , H , Heikkilä , H M , Soliymani , R , Käkelä , R , Saksi , J , Jauhiainen , M , Grabowski , G A , Kummu , O , Hörkkö , S , Baumann , M , Lindsberg , P J , Jokitalo , E , Kovanen , P T & Öörni , K 2018 , ' Extracellular Lipids Accumulate in Human Carotid Arteries as Distinct Three-Dimensional Structures and Have Proinflammatory Properties ' , The American Journal of Pathology , vol. 188 , no. 2 , pp. 525-538 . https://doi.org/10.1016/j.ajpath.2017.09.019
Title: | Extracellular Lipids Accumulate in Human Carotid Arteries as Distinct Three-Dimensional Structures and Have Proinflammatory Properties |
Author: | Lehti, Satu; Nguyen, Su D.; Belevich, Ilya; Vihinen, Helena; Heikkilä, Hanna M.; Soliymani, Rabah; Käkelä, Reijo; Saksi, Jani; Jauhiainen, Matti; Grabowski, Gregory A.; Kummu, Outi; Hörkkö, Sohvi; Baumann, Marc; Lindsberg, Perttu J.; Jokitalo, Eija; Kovanen, Petri T.; Öörni, Katariina |
Contributor organization: | Electron Microscopy Institute of Biotechnology Research Programme for Molecular Neurology Perttu Lindsberg / Principal Investigator Research Programs Unit Medicum Department of Biochemistry and Developmental Biology Biosciences Functional Lipidomics Group Physiology and Neuroscience (-2020) Marc Baumann / Principal Investigator Clinicum Department of Neurosciences Neurologian yksikkö HUS Neurocenter |
Date: | 2018-02 |
Language: | eng |
Number of pages: | 14 |
Belongs to series: | The American Journal of Pathology |
ISSN: | 0002-9440 |
DOI: | https://doi.org/10.1016/j.ajpath.2017.09.019 |
URI: | http://hdl.handle.net/10138/311770 |
Abstract: | Lipid accumulation is a key characteristic of advancing atherosclerotic lesions. Herein, we analyzed the ultrastructure of the accumulated Lipids in endarterectomized human carotid atherosclerotic plaques using three-dimensional (3D) electron microscopy, a method never used in this context before. 3D electron microscopy revealed intracellular lipid droplets and extracellular Lipoprotein particles. Most of the particles were aggregated, and some connected to needle-shaped or sheet-like cholesterol crystals. Proteomic analysis of isolated extracellular Lipoprotein particles revealed that apolipoprotein B is their main protein component, indicating their origin from low-density lipoprotein, intermediate-density Lipoprotein, very-Low-density lipoprotein, lipoprotein (a), or chylomicron remnants. The particles also contained small exchangeable apolipoproteins, complement components, and immunoglobulins. Lipidomic analysis revealed differences between plasma lipoproteins and the particles, thereby indicating involvement of lipolytic enzymes in their generation. Incubation of human monocyte-derived macrophages with the isolated extracellular lipoprotein particles or with plasma lipoproteins that had been Lipolytically modified in vitro induced intracellular Lipid accumulation and triggered inflammasome activation in them. Taken together, extracellular Lipids accumulate in human carotid plaques as distinct 3D structures that include aggregated and fused lipoprotein particles and cholesterol crystals. The particles originate from plasma lipoproteins, show signs of lipolytic modifications, and associate with cholesterol crystals. By inducing intracellular cholesterol accumulation (ie, foam cell formation) and inflammasome activation, the extracellular lipoprotein particles may actively enhance atherogenesis. |
Subject: |
LOW-DENSITY-LIPOPROTEIN
HUMAN ATHEROSCLEROTIC LESIONS NLRP3 INFLAMMASOME ACTIVATION FOAM CELL-FORMATION SECRETORY SPHINGOMYELINASE CHOLESTEROL CRYSTALS PROTEOGLYCAN-BINDING ELECTRON-MICROSCOPY HUMAN MONOCYTES DEFICIENT MICE 3111 Biomedicine |
Peer reviewed: | Yes |
Rights: | cc_by_nc_nd |
Usage restriction: | openAccess |
Self-archived version: | acceptedVersion |
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