Extracellular Lipids Accumulate in Human Carotid Arteries as Distinct Three-Dimensional Structures and Have Proinflammatory Properties

Show full item record



Permalink

http://hdl.handle.net/10138/311770

Citation

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: University of Helsinki, Electron Microscopy
University of Helsinki, Institute of Biotechnology
University of Helsinki, Research Programme for Molecular Neurology
University of Helsinki, Medicum
University of Helsinki, Biosciences
University of Helsinki, Research Programme for Molecular Neurology
University of Helsinki, Medicum
University of Helsinki, Clinicum
University of Helsinki, Institute of Biotechnology
University of Helsinki, Wihuri Research Institute
University of Helsinki, Biosciences
Date: 2018-02
Number of pages: 14
Belongs to series: The American Journal of Pathology
ISSN: 0002-9440
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
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
Lehti_2018.pdf 3.848Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record