Department of Medicine, Division of Infectious Diseases and Immunology
Biochemistry, Biophysics, and Structural Biology | Cardiovascular Diseases | Cellular and Molecular Physiology | Lipids | Virus Diseases
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.
Cholesterol, Macaque, Crystals, Lipids, Macrophages, Atherosclerosis, Diet, Fats
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Copyright: © 2021 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
Park MH, Suhalim JL, Elmastour F, Singha SK, Imafuku T, Venkatnarayan R, Christ A, Grebe A, Oppelt SA, Sviridov D, Bukrinsky M, Latz E, Potma EO, Fitzgerald ML. Non-linear optical imaging of atherosclerotic plaques in the context of SIV and HIV infection prominently detects crystalline cholesterol esters. PLoS One. 2021 May 13;16(5):e0251599. doi: 10.1371/journal.pone.0251599. PMID: 33984028; PMCID: PMC8118308. Link to article on publisher's site
Park MH, Suhalim JL, Elmastour F, Singha SK, Imafuku T, Venkatnarayan R, Christ A, Grebe A, Oppelt SA, Sviridov D, Bukrinsky M, Latz E, Potma EO, Fitzgerald ML. (2021). Non-linear optical imaging of atherosclerotic plaques in the context of SIV and HIV infection prominently detects crystalline cholesterol esters. Open Access Publications by UMMS Authors. https://doi.org/10.1371/journal.pone.0251599. Retrieved from https://escholarship.umassmed.edu/oapubs/4759
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