| Title: |
13 PHD1 deficiency promotes an atheroprotective metabolic phenotype. |
| Authors: |
Marsch, E; Demandt, J; Theelen, T; Gijbels, MJ; Rensen, PCN; Carmeliet, P; Fisher, EA; Biessen, EAL; Daemen, MJAP; Sluimer, JC |
| Source: |
Cardiovascular Research; Jul2014, Vol. 103 Issue suppl_1, pS2-S2, 1p |
| Subject Terms: |
METABOLIC disorders; OXYGEN detectors; HYDROXYLASES; GLYCOLYSIS; BLOOD sugar; OXYGEN consumption |
| Abstract: |
Knockout of the oxygen-sensor HIF prolyl hydroxylase 1 (PHD1) was shown to switch metabolism towards glycolysis and reduced cellular oxygen consumption. As we recently showed a pro-atherosclerotic effect of plaque hypoxia, we hypothesised that reduced cellular oxygen consumption in PHD1 knockout mice alleviates atherosclerosis development.Low density lipoprotein receptor knockout (LDLr-/-, control) and LDLr-/-PHD1-/- mice (n=17 and 10, respectively) were placed on a western-type diet (WTD, 0.25 % cholesterol) for 8 weeks to induce atherosclerosis. Mice were injected with pimonidazole (100 mg/kg i.p.) prior to sacrifice to detect hypoxia in atherosclerotic plaques.Atherogenesis was attenuated in PHD1-/- mice, as shown by reduced aortic root plaque size (-35%, p=0.008, H&E) and necrotic core content (-38%, p=0.004, H&E). Plaque hypoxia was significantly reduced in PHD1-/- mice (-32%, p=0.02), despite unchanged MAC3 macrophage content, suggestive of reduced macrophage oxygen consumption. PHD1 deficiency led to significantly lowered plasma cholesterol (-21%, p |
| : |
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| Database: |
Complementary Index |