Table 4.
Abnormalities of fatty acid synthesis/oxidation in pulmonary hypertension
| Sources | Parameters | References |
|---|---|---|
| Human data | ||
| PAEC in vitro |
↓13C-α-ketoglutarate (αKG) from 13C-long chain fatty acids (LCFAs), ↓Acetyl-CoA acetyltransferase (ACAT)2 by global proteomics, ↑Enoyl-CoA delta isomerase (ECI)1 by global proteomics |
(12, 16) |
| Lung |
↑Carnitine, dicarboxylic acid, and long- and medium-chain free fatty acid products including caproate, caprylate, myristate, and palmitoleate by metabolomics, ↑Adrenate [a pro-thrombotic lipid that can cause obstructions] by metabolomics, ↑Expression of genes coding the enzymes fatty acetyl CoA L1 (ACSL1) and Acetyl CoA Carboxylase 1 (ACACA) by gene microarray |
(34) |
| Right ventricle |
↓Fatty acid uptake by 123I-labeled l5-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) single-photon emission computerized tomography (SPECT), ↓Fatty acid oxidation by gene microarray analyses, ↓Long-chain acylcarnitine by liquid chromatography/mass spectrometric analysis, ↑Lipid content by oil red O staining, ↑Ceramide by liquid chromatography/mass spectrometric analysis, ↑Triglycerides by cardiac imaging with proton spectroscopy |
(39, 60, 62, 64) |
| Plasma |
↑Free fatty acids by enzymatic assay, ↑Long-chain acylcarnitines by liquid chromatography/mass spectrometric analysis |
(64) |
| Animal models | ||
| Shunt lambs | ||
| Lung | ↑Acylcarnitines by FPLC | (40) |
| MCT rats | ||
| PASMC in vitro | ↑Carnitine palmitoyltransferase (CPT)1 by Western blot and immunofluorescence | (63) |
| Lung | ↑CPT1 and CD36 mRNA by qRT-PCR and protein by Western blot | (44, 63) |
| Right ventricle |
↑CPT1 and CD36 mRNA by qRT-PCR and protein by Western blot, ↑Myocardial lipid peroxidation in right ventricle in late stage PH by thiobarbituric acid reactive substances (TBARS) assay |
(44, 58, 63) |
| Severe pulmonary hypertension (SPH) ratsa | ||
| Right ventricle | ↓14-(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (18F-FTHA) [fatty acid analog] uptake | (59) |
| BMPR2−/− miceb | ||
| Right ventricle |
↓Fatty acid β-oxidation of palmitate by oxygen consumption measurement using Oroboros O2k Oxygraph, ↑Fatty acid uptake by 14C-palmitate, ↑CD36 fatty acid transporter molecule by immunofluorescence and Western blot analyses, ↑Fatty acid metabolites by metabolomics, ↑Lipid accumulation in the form of triglycerides, diacylglycerol, and ceramides by metabolomics, ↑Lipid by oil red O staining |
(39, 56, 61, 64) |
| CAV1−/− micec | ||
| Heart |
↓Triglycerides, fatty acids, and cholesterol measured enzymatically, ↑Lipid uptake by measure the uptake of 14C-palmitate, ↑14C-palmitate oxidation, ↑cAMP by cAMP [3H] assay |
(57) |
| eNOS−/− mice | ||
| Brown adipocytes or brown adipose tissue |
↑Lipid droplets in adipocytes by oil red O staining |
(52) |
a
SPH rats, SPH induced by treatment with the VEGF receptor inhibitor SU5416 and under hypoxia;
b
BMPR2−/− mice, with BMPR2 knockout, do not develop pulmonary hypertension spontaneously but are more susceptible to hypoxic or chemically induced PH
c
CAV1−/− mice, with caveolin-1 knockout with pulmonary hypertension and left ventricular hypertrophy