Table 3.
Decreased glucose oxidation and abnormal mitochondria in pulmonary hypertension
| Sources | Parameters | References |
|---|---|---|
| Human data | ||
| PAEC in vitro |
↓Oxygen consumption with a Seahorse XF24 analyzer, ↓Oxygen consumption under state 3 and state 4 respiration using the classical method of circulator chambers and a 5300A biological oxygen monitor and Clark-type polarographic oxygen electrode, ↓Complex IV activity by spectrophotometry and mitochondrial dehydrogenase activity by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay, ↓mtDNA by Southern blot, ↓Mitochondrial numbers by quantitation of mitochondria in electron microscopy images of cells |
(10, 12) |
| PASMC in vitro | ↓ Mitochondria by immunofluorescence | (14, 15) |
| Small pulmonary arteries | ↓Complex I by immunofluorescence | (14, 15) |
| Animal models | ||
| Shunt lambs | ||
| Lung | ↑Uncoupling protein (UCP)2-expression by Western blot analyses | (40) |
| Chickens with pulmonary hypertension syndromea | ||
| Lung | ↓Oxygen consumption under state 3 and state 4 respiration using the classical method | (50, 51) |
| Breast and heart muscle |
↓Oxygen consumption under state 3 respiration using the classical method, ↓Complex I activity by spectrophotometry, ↑Succinate metabolism |
(50, 51) |
| Fawn hooded rats | ||
| PASMC |
↓Complexes I by immunofluorescence, Small, dense, dysmorphic mitochondria (swollen cristae) by transmission electron microscopy |
(14, 15) |
| Small rat pulmonary arteries | ↓Complexes I, III, and IV by Western blot analyses | (14, 15) |
| Monocrotaline (MCT) rats | ||
| Right ventricle |
↓Oxygen consumption by high-resolution respirometry, ↓14C-glucose oxidation |
(42, 43) |
| Endothelial nitric oxide synthase (eNOS)−/− miceb | ||
| Lung | ↓Oxygen consumption with Oxymax metabolic chamber | (52) |
| Brain, liver, heart tissue and brown adipocytes or brown adipose tissue |
↓Complex IV and cytochrome complex (Cyt c) by Western blot analyses, ↓UCP1 and peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α, nuclear factor erythroid 2–related factor (NRF)-1, and mitochondrial transcription factor A (mtTFA) mRNA by qRT-PCR, ↓mtDNA by Southern blot |
(52) |
| Soleus muscles | ↓Oxygen consumption by a Clark electrode in an oxygraphic cell | (53) |
| Brown adipocytes or brown adipose tissue | ↓Number of mitochondria by MitoTracker fluorescence | (52) |
a
Chickens with pulmonary hypertension syndrome and increased RV/total ventricle weight ratio; chickens developed pulmonary hypertension syndrome under cool temperatures combined with feed to support rapid growth rate;
b
eNOS−/− mice, with eNOS knockout