Table 4.
Pi-induced ROS production is a possible risk factor for cardiovascular disease.
| Cell Type or Tissue Sample | Results Observed | Pi Treatment | Pharmacologic Effect |
|---|---|---|---|
| Bovine aortic endothelial cells [40,41]. | Increased ROS production [40]. | 2.8 mM Pi for 80 min. | Inhibition by NOX inhibitor (10 μM DPI). |
| Reduced NO production [40]. | 2.8 mM Pi for 800 s. | - | |
| Increased PKC activity [41]. | 3 mM Pi for 15 min. | Inhibition by 200 μM PFA. | |
| Bovine aortic smooth muscle cells [42]. | Increased mitochondrial membrane potential. | 10 mM β-glycerophosphate (BGP) for 2 days. | - |
| Increased ROS production | 10 mM BGP for 2 days. | Inhibition by a respiratory chain inhibitor (rotenone, 10 μM) or carbonyl cyanide m-chlorophenyl hydrazone (CCCP; 10 μM). | |
| Increased smooth muscle cells calcification and bone-related markers. | 10 mM BGP for 2 days. | Inhibition by 10 μM rotenone and 10 μM CCCP. | |
| Bovine aortic smooth muscle cells from male C57BL6N mice [43]. | Decreased mitochondrial membrane potential. | 3.6 mM Pi for 4 days. | - |
| Decreased ATP production. | 3.6 mM Pi for 4 days. | Inhibition by 300 μM α-lipoic acid. | |
| Increased ROS production. | 3.6 mM Pi for 4 days. | Inhibition by 300 μM α-lipoic acid. | |
| Increased cells apoptosis. | 3.6 mM Pi for 4 days. | Inhibition by 300 μM α-lipoic acid. | |
| Increased smooth muscle calcification. | 3.6 mM Pi for 4 days. | Inhibition by 300 μM α-lipoic acid. | |
| Human endothelial cells (EAhy926 cells and GM-7373 cells) [44]. | Decreased mitochondrial membrane potential. | 2.5–5 mM Pi and 2.8 mM Ca2+ for 2 h. | Inhibition by a Pi transporter inhibitor (1 mM PFA). |
| Increased ROS production. | 2.5 mM Pi and 2.8 mM Ca2+ for 75 min. | Inhibition by a superoxide scavenger (3-dimethyl-2-thiourea—DMTU, 10 mM). | |
| Increased cell apoptosis. | 5 mM Pi and 2.8 mM Ca2+ for 24 h. | Inhibition by a general caspase inhibitor (Z-VAD-FMK, 100 μM). | |
| Human umbilical vein endothelial cells (HUVECs) and endothelial cells of C57Bl/6 mice [46]. | Impairment of the PPARα/LKB1/AMPK/NOS pathway. | 3 mM Pi for 48 h. | Inhibition by a AMPK agonist (AIACR, 100 μM), PPARα agonist (100 μM WY-14643), PGC-1α inhibitor (SR-18292, 50 µM) and PFA (0.5 mM). |
| Decreased the mitochondrial membrane potential. | 3 mM Pi for 48 h. | Inhibition by AIACR (100 μM), SR-18292 (50 µM). | |
| Increased mitochondrial ROS production. | 3 mM Pi for 48 h. | Inhibition by AIACR (100 μM), SR-18292 (50 µM), cytoplasmic ROS scavenger (tempol, 100 µM) and mitochondrial ROS scavenger (mito-tempo, 100 µM). | |
| Reduced NO production. | 3 mM Pi for 48 h. | Inhibition by AIACR (100 μM), WY-14643 (100 μM). | |
| Increased relaxation in mesenteric arteries. | Mice fed high Pi diet (1.3% phosphate). | Inhibition by AIACR (100 μmol/L), compound C (1 μmol/L, AMPK inhibitor) and WY-14643 (100 μmol/L in drinking water, 2 weeks). |