Non-linear optical imaging of atherosclerotic plaques in the context of SIV and HIV infection prominently detects crystalline cholesterol esters.
Animals
Cholesterol Esters
/ analysis
HIV
/ isolation & purification
HIV Infections
/ complications
Macaca
Male
Mice
Mice, Inbred C57BL
Optical Imaging
Plaque, Atherosclerotic
/ complications
RAW 264.7 Cells
Simian Acquired Immunodeficiency Syndrome
/ complications
Simian Immunodeficiency Virus
/ isolation & purification
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
04
12
2020
accepted:
28
04
2021
entrez:
13
5
2021
pubmed:
14
5
2021
medline:
26
10
2021
Statut:
epublish
Résumé
Chronic HIV infection may exacerbate atherosclerotic vascular disease, which at advanced stages presents as necrotic plaques rich in crystalline cholesterol. Such lesions can catastrophically rupture precipitating myocardial infarct and stroke, now important causes of mortality in those living with HIV. However, in this population little is known about plaque structure relative to crystalline content and its chemical composition. Here, we first interrogated plaque crystal structure and composition in atherosclerotic SIV-infected macaques using non-linear optical microscopy. By stimulated Raman scattering and second harmonic generation approaches both amorphous and crystalline plaque lipid was detected and the crystal spectral profile indicated a cholesterol ester (CE) dominated composition. Versus controls, SIV+ samples had a greater number of cholesterol crystals (CCs), with the difference, in part, accounted for by crystals of a smaller length. Given the ester finding, we profiled HIV+ plaques and also observed a CE crystalline spectral signature. We further profiled plaques from Ldlr-/- mice fed a high fat diet, and likewise, found CE-dominate crystals. Finally, macrophage exposure to CCs or AcLDL induced auto-fluorescent puncta that co-stained with the LC3B autophagy sensor. In aggregate, we show that atheromatous plaques from mice, macaques and humans, display necrotic cores dominated by esterified CCs, and that plaque macrophages may induce autophagic vesicle formation upon encountering CCs. These findings help inform our knowledge of plaque core lipid evolution and how the process may incite systemic inflammation.
Identifiants
pubmed: 33984028
doi: 10.1371/journal.pone.0251599
pii: PONE-D-20-38194
pmc: PMC8118308
doi:
Substances chimiques
Cholesterol Esters
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0251599Subventions
Organisme : NIDDK NIH HHS
ID : T32 DK007028
Pays : United States
Organisme : NIBIB NIH HHS
ID : P41 EB015890
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL140977
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL101274
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL112661
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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