[HTML][HTML] 18F-FDG imaging of human atherosclerotic carotid plaques reflects gene expression of the key hypoxia marker HIF-1α

SF Pedersen, M Græbe, AMF Hag… - American journal of …, 2013 - ncbi.nlm.nih.gov
American journal of nuclear medicine and molecular imaging, 2013ncbi.nlm.nih.gov
To investigate the association between gene expression of key molecular markers of
hypoxia and inflammation in atherosclerotic carotid lesions with 2-deoxy-2-[18 F] fluoro-D-
glucose (18 F-FDG) uptake as determined clinically by positron emission tomography (PET).
Studies using PET have demonstrated 18 F-FDG-uptake in patients with confirmed plaques
of the carotid artery. Inflammatory active or “vulnerable” plaques progressively increase in
bulk, develop necrotic cores, poor vessel-wall vascularization and become prone to hypoxia …
Abstract
To investigate the association between gene expression of key molecular markers of hypoxia and inflammation in atherosclerotic carotid lesions with 2-deoxy-2-[18 F] fluoro-D-glucose (18 F-FDG) uptake as determined clinically by positron emission tomography (PET). Studies using PET have demonstrated 18 F-FDG-uptake in patients with confirmed plaques of the carotid artery. Inflammatory active or “vulnerable” plaques progressively increase in bulk, develop necrotic cores, poor vessel-wall vascularization and become prone to hypoxia. We used quantitative polymerase-chain reaction (qPCR) to determine gene expression of hypoxia-inducible factor 1α (HIF-1α) and cluster of differentiation 68 (CD68) on plaques recovered by carotid endarterectomy (CEA) in 18 patients. Gene expression was compared with 18 F-FDG-uptake quantified as the maximum standardized uptake value (SUV max) on co-registered PET/computed tomography (CT) scans performed the day before CEA. Immunohistochemistry was used to validate target-gene protein expression. In univariate linear regression analysis HIF-1α was significantly correlated with 18 F-FDG-uptake (SUV max) as was CD68. A two-tailed Pearson regression model demonstrated that HIF-1α and CD68 gene expression co-variated and accordingly when entering the variables into multivariate linear regression models with SUV-values as dependent variables, HIF-1α was eliminated in the final models. 18 F-FDG-uptake (SUV max) is correlated with HIF-1α gene expression indicating an association between hypoxia and glucose metabolism in vivo. The marker of inflammation CD68 is also associated with 18 F-FDG-uptake (SUV max). As CD68 and HIF-1α gene expression co-variate their information is overlapping.
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