{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Demirdelen S"],"funding":["NHLBI NIH HHS"],"pagination":["1266-1276"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8935477"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["29(3)"],"pubmed_abstract":["<h4>Background</h4>Metabolic divergence of macrophages polarized into different phenotypes represents a mechanistically relevant target for non-invasive characterization of atherosclerotic plaques using positron emission tomography (PET). Carbon-11 (<sup>11</sup>C)-labeled acetate is a clinically available tracer which accumulates in atherosclerotic plaques, but its biological and clinical correlates in atherosclerosis are undefined.<h4>Methods and results</h4>Histological correlates of <sup>14</sup>C-acetate uptake were determined in brachiocephalic arteries of western diet-fed apoE<sup>-/-</sup> mice. The effect of polarizing stimuli on <sup>14</sup>C-acetate uptake was determined by proinflammatory (interferon-γ + lipopolysaccharide) vs inflammation-resolving (interleukin-4) stimulation of murine macrophages and human carotid endarterectomy specimens over 2 days. <sup>14</sup>C-acetate accumulated in atherosclerotic regions of arteries. CD68-positive monocytes/macrophages vs smooth muscle actin-positive smooth muscle cells were the dominant cells in regions with high vs low <sup>14</sup>C-acetate uptake. <sup>14</sup>C-acetate uptake progressively decreased in proinflammatory macrophages to 25.9 ± 4.5% of baseline (P < .001). A delayed increase in <sup>14</sup>C-acetate uptake was induced in inflammation-resolving macrophages, reaching to 164.1 ± 21.4% (P < .01) of baseline. Consistently, stimulation of endarterectomy specimens with interferon-γ + lipopolysaccharide decreased <sup>14</sup>C-acetate uptake to 66.5 ± 14.5%, while interleukin-4 increased <sup>14</sup>C-acetate uptake to 151.5 ± 25.8% compared to non-stimulated plaques (P < .05).<h4>Conclusions</h4>Acetate uptake by macrophages diverges upon proinflammatory and inflammation-resolving stimulation, which may be exploited for immunometabolic characterization of atherosclerosis."],"journal":["Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology"],"pubmed_title":["Divergence of acetate uptake in proinflammatory and inflammation-resolving macrophages: implications for imaging atherosclerosis."],"pmcid":["PMC8935477"],"funding_grant_id":["K08 HL144911","R01 HL146465"],"pubmed_authors":["Haddad J","Leers SA","Demirdelen S","Mannes PZ","Aral AM","Gomez D","Tavakoli S"],"additional_accession":[]},"is_claimable":false,"name":"Divergence of acetate uptake in proinflammatory and inflammation-resolving macrophages: implications for imaging atherosclerosis.","description":"<h4>Background</h4>Metabolic divergence of macrophages polarized into different phenotypes represents a mechanistically relevant target for non-invasive characterization of atherosclerotic plaques using positron emission tomography (PET). Carbon-11 (<sup>11</sup>C)-labeled acetate is a clinically available tracer which accumulates in atherosclerotic plaques, but its biological and clinical correlates in atherosclerosis are undefined.<h4>Methods and results</h4>Histological correlates of <sup>14</sup>C-acetate uptake were determined in brachiocephalic arteries of western diet-fed apoE<sup>-/-</sup> mice. The effect of polarizing stimuli on <sup>14</sup>C-acetate uptake was determined by proinflammatory (interferon-γ + lipopolysaccharide) vs inflammation-resolving (interleukin-4) stimulation of murine macrophages and human carotid endarterectomy specimens over 2 days. <sup>14</sup>C-acetate accumulated in atherosclerotic regions of arteries. CD68-positive monocytes/macrophages vs smooth muscle actin-positive smooth muscle cells were the dominant cells in regions with high vs low <sup>14</sup>C-acetate uptake. <sup>14</sup>C-acetate uptake progressively decreased in proinflammatory macrophages to 25.9 ± 4.5% of baseline (P < .001). A delayed increase in <sup>14</sup>C-acetate uptake was induced in inflammation-resolving macrophages, reaching to 164.1 ± 21.4% (P < .01) of baseline. Consistently, stimulation of endarterectomy specimens with interferon-γ + lipopolysaccharide decreased <sup>14</sup>C-acetate uptake to 66.5 ± 14.5%, while interleukin-4 increased <sup>14</sup>C-acetate uptake to 151.5 ± 25.8% compared to non-stimulated plaques (P < .05).<h4>Conclusions</h4>Acetate uptake by macrophages diverges upon proinflammatory and inflammation-resolving stimulation, which may be exploited for immunometabolic characterization of atherosclerosis.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jun","modification":"2024-11-12T01:37:30.163Z","creation":"2024-11-12T01:37:30.163Z"},"accession":"S-EPMC8935477","cross_references":{"pubmed":["33420659"],"doi":["10.1007/s12350-020-02479-5"]}}