Table 1.
Effect of mTOR inhibitor PP242 on human PAH PAVSMC deregulated metabolites
| PAH PAVSMCs | ||||||
|---|---|---|---|---|---|---|
| Biochemical name | Control | PAH | PAH/control ratio | Vehicle | PP242 | PP242/vehicle ratio |
| Eicosapentaenoate (EPA; 20:5n3) | 0.479 | 1.2577 | 2.63↑* | 1.1575 | 1.3281 | 1.15 |
| Docosahexaenoate (DHA; 22:6n3) | 0.6719 | 1.1076 | 1.65↑* | 1.1328 | 1.0652 | 0.94 |
| Caprylate (8:0) | 0.629 | 1.9576 | 3.11↑* | 1.7127 | 0.7639 | 0.45↓** |
| Bisphenol A monosulfate | 0.606 | 1.4518 | 2.4↑* | 1.5235 | 0.3854 | 0.25↓** |
| Penicillin G | 0.2923 | 2.5761 | 8.81↑* | 2.5431 | 0.2688 | 0.11↓** |
| N-acetylglucosamine 6-phosphate | 0.5371 | 1.4396 | 2.68↑# | 1.3159 | 1.3697 | 1.04 |
| Citrate | 0.935 | 1.6895 | 1.81↑# | 1.0616 | 0.6472 | 0.61↓** |
| Caprate (10:0) | 0.9623 | 1.3458 | 1.4↑# | 1.2588 | 0.8663 | 0.69↓## |
| Arachidonate (20:4n6) | 0.6341 | 1.0516 | 1.66↑# | 1.0401 | 1.2266 | 1.18 |
| Choline | 0.9411 | 1.1652 | 1.24↑# | 1.3329 | 0.9087 | 0.68↓** |
| Glycerophosphorylcholine (GPC) | 0.5603 | 1.2177 | 2.17↑# | 1.2177 | 1.3078 | 1.07 |
| Riboflavin (vitamin B2) | 0.4164 | 1.1935 | 2.87↑# | 1.2907 | 0.698 | 0.54 |
| Pyridoxine (vitamin B6) | 0.9501 | 1.4166 | 1.49↑# | 1.4069 | 0.6516 | 0.46↓** |
| N-acetylneuraminate | 1.4949 | 0.9071 | 0.61↓* | 0.974 | 1.1743 | 1.21 |
| Gluconate | 1.4773 | 0.5806 | 0.39↓* | 0.5666 | 1.6347 | 2.89↑** |
| Xylitol | 2.0647 | 0.6786 | 0.33↓* | 0.7505 | 1.6655 | 2.22↑** |
| Urate | 2.3562 | 0.7913 | 0.34↓* | 1.3067 | 0.8703 | 0.67 |
| Cytidine-3′-monophosphate (3′-CMP) | 1.8755 | 0.7057 | 0.38↓* | 0.6412 | 1.4894 | 2.32 |
| Pseudouridine | 1.7391 | 0.6058 | 0.44↓* | 0.7452 | 1.3515 | 1.81↑** |
| Adenosine 5′ diphosphoribose | 4.661 | 0.5081 | 0.3↓* | 0.4202 | 1.1663 | 2.78↑** |
| Cysteinylglycine | 1.7283 | 0.7535 | 0.35↓* | 0.6759 | 1.8305 | 2.71↑** |
| Aspartyltryptophan | 1.7118 | 0.5208 | 0.49↓* | 0.3178 | 1.7057 | 5.37↑** |
| Aspartylphenylalanine | 1.6649 | 0.5908 | 0.38↓* | 0.4835 | 1.7727 | 3.67↑** |
| Aspartate-glutamate | 1.3535 | 0.6626 | 0.49↓* | 0.7953 | 1.7233 | 2.17↑** |
| Beta-alanine | 2.3868 | 0.9075 | 0.38↓* | 1.0082 | 1.4353 | 1.42 |
| C-glycosyltryptophan | 2.3443 | 0.8296 | 0.35↓* | 0.8774 | 1.2138 | 1.38↑** |
| Pyroglutamine | 2.0257 | 0.9363 | 0.46↓* | 1.1066 | 1.1858 | 1.07 |
| Ribulose | 2.2799 | 0.8186 | 0.36↓# | 0.9362 | 1.4586 | 1.56↑## |
| UDP-glucuronate | 2.2888 | 0.5078 | 0.22↓# | 0.4717 | 0.7584 | 1.61↑## |
| Fructose | 1.2145 | 0.4937 | 0.41↓# | 0.7146 | 1.6642 | 2.33↑** |
| Docosatrienoate (22:3n3) | 1.5111 | 1.0544 | 0.7↓# | 1.0975 | 1.0558 | 0.96 |
| Scyllo-inositol | 2.3482 | 0.392 | 0.17↓# | 0.3547 | 0.5779 | 1.63 |
| 1-palmitoleoylglycerophosphoethanolamine | 1.3694 | 0.6247 | 0.46↓# | 0.77 | 1.0805 | 1.4↑## |
| Nicotinamide | 2.7705 | 1.0521 | 0.38↓# | 1.2287 | 0.898 | 0.73 |
| Aspartylvaline | 1.2538 | 0.6864 | 0.55↓# | 0.9112 | 1.6156 | 1.77↑## |
| Aspartylleucine | 1.4226 | 0.6961 | 0.49↓# | 0.6184 | 1.5914 | 2.57↑** |
| Cysteine | 1.1987 | 0.6932 | 0.58↓# | 0.4638 | 4.3122 | 9.3↑** |
| Homocysteine | 1.3576 | 0.8643 | 0.64↓# | 0.8831 | 1.8607 | 2.11↑** |
Note
Data are means from 5 subjects/group. Boldface indicates deregulated metabolites. Arrows indicate increased (↑) or decreased (↓) metabolite levels. Significance was based on the Welch 2-sample t test. mTOR: mammalian target of rapamycin; PAH: pulmonary arterial hypertension; PAVSMCs: pulmonary arterial vascular smooth muscle cells; UDP: uridine diphosphate.
*
P ≤ 0.05 for PAH versus control.
#
0.05 < P < 0.1 for PAH versus control.
**
P ≤ 0.05 for PP242-treated versus vehicle-treated.
##
0.05 < P < 0.1 for PP242-treated versus vehicle-treated.