2015
DOI: 10.1152/ajplung.00169.2015
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Severe pulmonary hypertension is associated with altered right ventricle metabolic substrate uptake

Abstract: In severe pulmonary hypertension (SPH), prior studies have shown an increase in right ventricle (RV) uptake of glucose, but it is unclear whether there is a change in the relative utilization of fatty acids. We hypothesized that in the RV in SPH, as in left ventricular (LV) failure, there is altered substrate utilization, with increased glucose uptake and decreased fatty acid uptake. SPH was induced in rats by treatment with the VEGF receptor inhibitor SU5416 and 3 wk of hypoxia (10% FiO2 ), followed by an add… Show more

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Cited by 48 publications
(37 citation statements)
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“…These observations in platelets are consistent with prior studies linking FAO to increased reserve capacity in cardiomyocytes (7,14). Our data also mirror prior studies in other tissues in PH demonstrating a decreased reliance on glucose oxidation (15) and increased FAO enzyme activity (13). The observed trend toward decreased PDH activity and increased CPT1 enzyme activity observed in the PH platelets provides an enzymatic basis for substrate switching.…”
Section: Discussionsupporting
confidence: 92%
See 1 more Smart Citation
“…These observations in platelets are consistent with prior studies linking FAO to increased reserve capacity in cardiomyocytes (7,14). Our data also mirror prior studies in other tissues in PH demonstrating a decreased reliance on glucose oxidation (15) and increased FAO enzyme activity (13). The observed trend toward decreased PDH activity and increased CPT1 enzyme activity observed in the PH platelets provides an enzymatic basis for substrate switching.…”
Section: Discussionsupporting
confidence: 92%
“…Notably, mitochondrial and metabolic aberrations are not confined to the pulmonary vasculature. Cardiac tissue and cells from animal models of PH have shown altered mitochondrial ETC enzyme expression, as well as changes in substrate utilization (12)(13)(14)(15)(16)(17), and increased expression of glycolytic enzymes has also been reported in the skeletal muscle of PH patients (18). Consistent with a central role for this glycolytic shift in PH pathogenesis, pharmacologic therapy that suppresses glycolysis while enhancing oxidative phosphorylation attenuates PH progression (10,15).…”
Section: Introductionmentioning
confidence: 94%
“…27 A recent study investigating RV metabolism in the Sugen5416/Hypoxia rat model found a significant decrease in RV FTHA uptake and an increase in RV FDG uptake at 8 weeks. 13 In comparison with these findings, the current study by Drozd et al showed a twofold increase in FTHA uptake at 5 weeks, which was slightly lower but still elevated at 8 weeks. Interestingly, in the current study, the increased FTHA uptake was not affected by macitentan therapy at this 8-week time point.…”
supporting
confidence: 48%
“…There is growing evidence from both animal studies 12,13 and clinical observations 14-16 that PAH is associated with increased RV FDG uptake compared to controls. In small cohorts of PAH patients, the left ventricle (LV) to RV FDG uptake ratio was shown to correlate well with pulmonary artery pressures 17 and RV ejection fraction.…”
mentioning
confidence: 99%
“…203,229). In the SuHx model of PH, severe RV dysfunction was associated with a shift in metabolic substrate utilization, measured via imaging for 2-deoxy-2-[ 18 F]fluoroglucose (glucose analog) and 14-(R,S)-[ 18 F]fluoro-6-thia-heptadecanoic acid (fatty acid analog), demonstrating increased glucose, and reduced fatty acid, uptake (96). These results were consistent with data in patients indicating increased RV glucose uptake that correlated with RV dysfunction (33,150,275).…”
Section: Pathways and Targetsmentioning
confidence: 99%