Mapping of the Glucose Metabolism Heterogeneity in Atherosclerosis: Correlation With 2-Deoxyglucose Uptake
Objective 2-Deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) is widely used for noninvasive imaging of atherosclerosis. However, knowledge about metabolic processes underlying [ 18 F]FDG uptake is mostly derived from in vitro cell culture studies, which cannot recapitulate the complexities of the plaque...
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SAGE Publishing
2024-09-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.1177/15353508241280573 |
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| author | Joseph Haddad MD Selim Demirdelen MD Clayton E. Barnes BS Steven A. Leers MD Sina Tavakoli MD, PhD |
| author_facet | Joseph Haddad MD Selim Demirdelen MD Clayton E. Barnes BS Steven A. Leers MD Sina Tavakoli MD, PhD |
| author_sort | Joseph Haddad MD |
| collection | DOAJ |
| description | Objective 2-Deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) is widely used for noninvasive imaging of atherosclerosis. However, knowledge about metabolic processes underlying [ 18 F]FDG uptake is mostly derived from in vitro cell culture studies, which cannot recapitulate the complexities of the plaque microenvironment. Here, we sought to address this gap by in situ mapping of the activity of selected major dehydrogenases involved in glucose metabolism in atherosclerotic plaques. Methods In situ activity of lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G6PD), succinate dehydrogenase (SDH), and isocitrate dehydrogenase (IDH) was assessed in plaques from murine aortic root and brachiocephalic arteries and human carotid arteries. High-resolution 2-deoxy-D-[1,2- 3 H]glucose ([ 3 H]2-deoxyglucose) autoradiography of murine brachiocephalic plaques was performed. Results LDH activity was heterogeneous throughout the plaques with the highest activity in medial smooth muscle cells (SMCs). G6PD activity was mostly confined to the medial layer and to a lesser extent to SMCs along the fibrous cap. SDH and IDH activities were minimal in plaques. Plaque regions with increased [ 3 H]2-deoxyglucose uptake were associated with a modestly higher LDH, but not G6PD, activity. Conclusions Our study reveals a novel aspect of the metabolic heterogeneity of the atherosclerotic plaques, enhancing our understanding of the complex immunometabolic biology that underlies [ 18 F]FDG uptake in atherosclerosis. |
| format | Article |
| id | doaj-art-deebf5928d5d4fefa22027c87f6dad29 |
| institution | OA Journals |
| issn | 1536-0121 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | SAGE Publishing |
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| series | Molecular Imaging |
| spelling | doaj-art-deebf5928d5d4fefa22027c87f6dad292025-08-20T01:47:48ZengSAGE PublishingMolecular Imaging1536-01212024-09-012310.1177/15353508241280573 Mapping of the Glucose Metabolism Heterogeneity in Atherosclerosis: Correlation With 2-Deoxyglucose UptakeJoseph Haddad MD0Selim Demirdelen MD1 Clayton E. Barnes BS2Steven A. Leers MD3Sina Tavakoli MD, PhD4 Departments of Radiology, Division of Cardiothoracic Imaging, , Pittsburgh, PA, USA Departments of Radiology, Division of Cardiothoracic Imaging, , Pittsburgh, PA, USA Departments of Radiology, Division of Cardiothoracic Imaging, , Pittsburgh, PA, USA Departments of Surgery, Division of Vascular Surgery, , Pittsburgh, PA, USA Heart, Lung, Blood, and Vascular Medicine Institute, UPMC Department of Medicine, Pittsburgh, PA, USA Objective 2-Deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) is widely used for noninvasive imaging of atherosclerosis. However, knowledge about metabolic processes underlying [ 18 F]FDG uptake is mostly derived from in vitro cell culture studies, which cannot recapitulate the complexities of the plaque microenvironment. Here, we sought to address this gap by in situ mapping of the activity of selected major dehydrogenases involved in glucose metabolism in atherosclerotic plaques. Methods In situ activity of lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G6PD), succinate dehydrogenase (SDH), and isocitrate dehydrogenase (IDH) was assessed in plaques from murine aortic root and brachiocephalic arteries and human carotid arteries. High-resolution 2-deoxy-D-[1,2- 3 H]glucose ([ 3 H]2-deoxyglucose) autoradiography of murine brachiocephalic plaques was performed. Results LDH activity was heterogeneous throughout the plaques with the highest activity in medial smooth muscle cells (SMCs). G6PD activity was mostly confined to the medial layer and to a lesser extent to SMCs along the fibrous cap. SDH and IDH activities were minimal in plaques. Plaque regions with increased [ 3 H]2-deoxyglucose uptake were associated with a modestly higher LDH, but not G6PD, activity. Conclusions Our study reveals a novel aspect of the metabolic heterogeneity of the atherosclerotic plaques, enhancing our understanding of the complex immunometabolic biology that underlies [ 18 F]FDG uptake in atherosclerosis.https://doi.org/10.1177/15353508241280573 |
| spellingShingle | Joseph Haddad MD Selim Demirdelen MD Clayton E. Barnes BS Steven A. Leers MD Sina Tavakoli MD, PhD Mapping of the Glucose Metabolism Heterogeneity in Atherosclerosis: Correlation With 2-Deoxyglucose Uptake Molecular Imaging |
| title | Mapping of the Glucose Metabolism Heterogeneity in Atherosclerosis: Correlation With 2-Deoxyglucose Uptake |
| title_full | Mapping of the Glucose Metabolism Heterogeneity in Atherosclerosis: Correlation With 2-Deoxyglucose Uptake |
| title_fullStr | Mapping of the Glucose Metabolism Heterogeneity in Atherosclerosis: Correlation With 2-Deoxyglucose Uptake |
| title_full_unstemmed | Mapping of the Glucose Metabolism Heterogeneity in Atherosclerosis: Correlation With 2-Deoxyglucose Uptake |
| title_short | Mapping of the Glucose Metabolism Heterogeneity in Atherosclerosis: Correlation With 2-Deoxyglucose Uptake |
| title_sort | mapping of the glucose metabolism heterogeneity in atherosclerosis correlation with 2 deoxyglucose uptake |
| url | https://doi.org/10.1177/15353508241280573 |
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