Thoracic [18F]fluorodeoxyglucose uptake measured by positron emission tomography/computed tomography in pulmonary hypertension

Frille, Armin; Steinhoff, Karen Geva; Hesse, Swen; Grachtrup, Sabine; Wald, Alexandra; Wirtz, Hubert; Sabri, Osama; Seyfarth, HJ

doi:10.1097/md.0000000000003976

Cited by 9 publications

(5 citation statements)

References 29 publications

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“…The switch from mitochondrial respiration to glycolysis, known as the "Warburg effect" when it happens under normoxic conditions, is well described for cancer cells and has also been confirmed to occur in pulmonary vascular cells isolated from PAH patients and animals (59,61). The pulmonary and RV L439 RAGE/IMPA1 INTERACTION IN PULMONARY HYPERTENSION glucose uptake measured by positron emission tomography (PET) was found to be elevated in PAH patients compared with healthy controls and correlated with the severity of PAH (11,49,62). In this study, we confirmed that the membrane translocation of two main glucose transporters, GLUT1 and GLUT4, was significantly increased in the lungs of animals with PAH, although the profile of this alteration for each transporter was different.…”

Section: Discussionmentioning

confidence: 94%

Inositol monophosphatase 1 as a novel interacting partner of RAGE in pulmonary hypertension

Rafikov

McBride

Zemskova

et al. 2019

American Journal of Physiology-Lung Cellular and Molecular Phys

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Pulmonary arterial hypertension (PAH) is a lethal disease characterized by progressive pulmonary vascular remodeling. The receptor for advanced glycation end products (RAGE) plays an important role in PAH by promoting proliferation of pulmonary vascular cells. RAGE is also known to mediate activation of Akt signaling, although the particular molecular mechanism remains unknown. This study aimed to identify the interacting partner of RAGE that could facilitate RAGE-mediated Akt activation and vascular remodeling in PAH. The progressive angioproliferative PAH was induced in 24 female Sprague-Dawley rats ( n = 8/group) that were randomly assigned to develop PAH for 1, 2, or 5 wk [right ventricle systolic pressure (RVSP) 56.5 ± 3.2, 63.6 ± 1.6, and 111.1 ± 4.5 mmHg, respectively, vs. 22.9 ± 1.1 mmHg in controls]. PAH triggered early and late episodes of apoptosis in rat lungs accompanied by RAGE activation. Mass spectrometry analysis has identified IMPA1 as a novel PAH-specific interacting partner of RAGE. The proximity ligation assay (PLA) confirmed the formation of RAGE/IMPA1 complex in the pulmonary artery wall. Activation of IMPA1 in response to increased glucose 6-phosphate (G6P) is known to play a critical role in inositol synthesis and recycling. Indeed, we confirmed a threefold increase in G6P ( P = 0.0005) levels in lungs of PAH rats starting from week 1 that correlated with accumulation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3), membrane translocation of PI3K, and a threefold increase in membrane Akt levels ( P = 0.02) and Akt phosphorylation. We conclude that the formation of the newly discovered RAGE-IMPA1 complex could be responsible for the stimulation of inositol pathways and activation of Akt signaling in PAH.

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Section: Discussionmentioning

confidence: 94%

Inositol monophosphatase 1 as a novel interacting partner of RAGE in pulmonary hypertension

Rafikov

McBride

Zemskova

et al. 2019

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…The glycolytic switch of metabolism in pulmonary vasculature is a well-accepted and characterized phenomenon in PAH. It was shown with a PET scanning of PAH patients that increased glycolysis in lungs and RV, similar to glycolytic changes seen in the tumors of cancer patients, correlates with the presence and severity of PAH [ 44 , 45 ]. However, there is still debate whether the glycolytic switch is secondary to electron transport chain dysfunction or is upregulated due to pathologic normoxic HIF1a signaling activation.…”

Section: Discussionmentioning

confidence: 99%

Recurrent inhibition of mitochondrial complex III induces chronic pulmonary vasoconstriction and glycolytic switch in the rat lung

et al. 2018

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BackgroundPulmonary arterial hypertension (PAH) is a fatal disease; however, the mechanisms directly involved in triggering and the progression of PAH are not clear. Based on previous studies that demonstrated a possible role of mitochondrial dysfunction in the pathogenesis of PAH, we investigated the effects of chronic inhibition of mitochondrial function in vivo in healthy rodents.MethodsRight ventricle systolic pressure (RVSP) was measured in female rats at baseline and up to 24 days after inhibition of mitochondrial respiratory Complex III, induced by Antimycin A (AA, 0.35 mg/kg, given three times starting at baseline and then days 3 and 6 as a bolus injection into the right atrial chamber).ResultsRodents exposed to AA demonstrated sustained increases in RVSP from days 6 through 24. AA-exposed rodents also possessed a progressive increase in RV end-diastolic pressure but not RV hypertrophy, which may be attributed to either early stages of PAH development or to reduced RV contractility due to inhibition of myocardial respiration. Protein nitration levels in plasma were positively correlated with PAH development in AA-treated rats. This finding was strongly supported by results obtained from PAH humans where plasma protein nitration levels were correlated with markers of PAH severity in female but not male PAH patients. Based on previously reported associations between increased nitric oxide production levels with female gender, we speculate that in females with PAH mitochondrial dysfunction may represent a more deleterious form, in part, due to an increased nitrosative stress development. Indeed, the histological analysis of AA treated rats revealed a strong perivascular edema, a marker of pulmonary endothelial damage. Finally, AA treatment was accompanied by a severe metabolic shift toward glycolysis, a hallmark of PAH pathology.ConclusionsChronic mitochondrial dysfunction induces the combination of vascular damage and metabolic reprogramming that may be responsible for PAH development. This mechanism may be especially important in females, perhaps due to an increased NO production and nitrosative stress development.

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“…On previous studies, clinical risk factors for cardiovascular disease including hypertension, diabetes mellitus, and dyslipidemia have been known to be affect FDG uptake of the myocardium [37][38][39]. Therefore, in the present study, we also compared myocardial FDG uptake according to the history of hypertension, diabetes mellitus, and dyslipidemia.…”

Section: Discussionmentioning

confidence: 93%

Relationship between Changes in Myocardial F-18 Fluorodeoxyglucose Uptake and Radiation Dose after Adjuvant Three-Dimensional Conformal Radiotherapy in Patients with Breast Cancer

Lee

Kim

et al. 2020

JCM

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This study aimed to assess the relationship between radiation dose and changes in the irradiated myocardial F-18 fluorodeoxyglucose (FDG) uptake after radiotherapy (RT) in breast cancer patients. The data of 55 patients with left and 48 patients with right breast cancer who underwent curative surgical resection and adjuvant three-dimensional conformal RT and staging (PET1), post-adjuvant chemotherapy (PET2), post-RT (PET3), and surveillance (PET4) FDG positron emission tomography/computed tomography (PET/CT) were retrospectively reviewed. The median interval between PET1 and curative surgical resection, between the end of adjuvant chemotherapy and PET2, between the end of RT and PET3, and between the end of RT and PET4 were five days, 13 days, 132 days, and 353 days, respectively. The myocardial-to-blood pool uptake ratio was measured in all patients. For patients with left breast cancer, the 30 Gy-(30 Gy) and 47.5 Gy-irradiated myocardium-to-low-irradiated myocardium (47.5 Gy) FDG uptake ratios were additionally measured. There were no differences in the myocardial-to-blood pool uptake ratios between left and right breast cancer on all PET scans. For left breast cancer, higher 30 Gy and 47.5 Gy uptake ratios were observed on PET3 than on PET1 and PET2. Both uptake ratios decreased on PET4 compared to PET3, but, were still higher compared to PET1. On PET3 and PET4, the 47.5 Gy were higher than the 30 Gy uptake ratios, while there were no differences between them on PET1 and PET2. Although the whole myocardium FDG uptake showed no significant change, the irradiated myocardium FDG uptake significantly increased after RT and was related to radiation dose to the myocardium in breast cancer patients. These results might be an imaging evidence that supports the increased risk of heart disease after RT in patients with left breast cancer.

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Thoracic [18F]fluorodeoxyglucose uptake measured by positron emission tomography/computed tomography in pulmonary hypertension

Abstract: Supplemental Digital Content is available in the text

Cited by 9 publications

References 29 publications

Inositol monophosphatase 1 as a novel interacting partner of RAGE in pulmonary hypertension

Inositol monophosphatase 1 as a novel interacting partner of RAGE in pulmonary hypertension

Recurrent inhibition of mitochondrial complex III induces chronic pulmonary vasoconstriction and glycolytic switch in the rat lung

Relationship between Changes in Myocardial F-18 Fluorodeoxyglucose Uptake and Radiation Dose after Adjuvant Three-Dimensional Conformal Radiotherapy in Patients with Breast Cancer

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