Paraoxonase-1 Inhibits Oxidized Low-Density Lipoprotein-Induced Metabolic Alterations and Apoptosis in Endothelial Cells: A Nondirected Metabolomic Study
Table 1
Heat map of metabolites showing statistically significant differences between groups.
Pathway
Metabolite
L/C*
O/C*
O/L*
OH/O*
KO/O*
KO/OH*
Glycine, serine, and threonine metabolism
Threonine
1.40
0.80
0.57
0.96
1.10
1.16
Glutamate metabolism
N-acetylglutamate
1.14
0.84
0.73
1.10
0.92
0.83
Phenylalanine and tyrosine metabolism
Phenylalanine
1.12
0.63
0.56
1.41
1.19
0.84
Tyrosine
1.11
0.62
0.56
1.57
1.37
0.87
Valine, leucine, and isoleucine metabolism
Isoleucine
1.36
0.65
0.48
1.57
1.38
0.88
Leucine
1.09
0.70
0.64
1.25
1.07
0.85
Valine
1.26
0.72
0.57
1.18
1.08
0.91
Urea cycle; arginine-, proline-, metabolism
Praline
1.18
0.89
0.75
0.92
0.97
1.05
Gamma-glutamyl peptides
Gamma-glutamyl-leucine
0.73
0.87
1.19
1.09
1.48
1.36
Amino-sugar metabolism
Fucose
0.72
0.76
1.05
1.25
1.06
0.85
Fructose, mannose, galactose, starch, and sucrose metabolism
Galactose
0.37
0.94
2.58
1.04
0.73
0.7
Mannose-6-phosphate
0.64
2.21
3.44
1.01
0.87
0.87
Glucose-6-phosphate
0.33
2.06
6.20
1.22
1.17
0.96
Fructose-6-phosphate
0.50
2.50
5.01
1.13
0.94
0.83
2-phosphoglycerate
2.28
0.67
0.29
2.17
1.05
0.48
3-phosphoglycerate
1.62
0.42
0.26
2.92
1.94
0.67
1,3-dihydroxyacetone
0.85
0.98
1.15
0.80
0.60
0.75
Phosphoenolpyruvate
1.06
0.23
0.22
4.66
3.05
0.66
Nucleotide sugars, pentose metabolism
Gluconate
0.43
0.89
2.07
1.06
0.86
0.81
TCA cycle
Fumarate
1.35
0.84
0.62
1.10
1.12
1.02
Malate
1.31
0.89
0.68
1.21
1.07
0.88
Oxidative phosphorylation
Acetyl phosphate
1.00
1.12
1.12
0.84
0.59
0.70
Phosphate
0.96
1.45
1.52
0.89
0.70
0.78
Medium chain fatty acid
Laurate (12 : 0)
0.98
1.15
1.17
0.92
0.74
0.81
Fatty acid, dicarboxylate
Undecanedioate
1.28
1.52
1.19
2.55
0.70
0.28
Glycerolipid metabolism
Ethanolamine
1.00
0.68
0.68
1.28
1.55
1.21
Choline
1.07
0.84
0.78
1.29
1.25
0.96
Glycerol 3-phosphate
1.54
0.31
0.20
4.13
2.87
0.69
Glycerophosphorylcholine
0.60
1.17
1.97
0.80
0.78
0.97
Purine metabolism, adenine containing
Adenosine 3′-monophosphate
2.38
0.73
0.31
1.70
1.09
0.64
Pyrimidine metabolism, uracil containing
Uracil
1.22
0.48
0.40
1.94
1.91
0.99
Uridine 5′-monophosphate
0.50
1.19
2.38
0.84
0.92
1.10
Pantothenate and CoA metabolism
Pantothenate
0.98
0.87
0.89
1.19
1.13
0.95
Riboflavin metabolism
Riboflavin (Vitamin B2)
0.68
0.76
1.11
1.15
1.11
0.97
Benzoate metabolism
4-hydroxy catechol
1.23
1.37
1.11
0.79
0.43
0.54
Chemicals
Glycolate (hydroxyacetate)
1.12
1.55
1.38
0.47
0.77
1.64
Glycerol 2-phosphate
0.98
0.65
0.67
1.96
1.11
0.57
Endothelial cells were incubated over 24 h with 50 mg/L isolated human LDL (L); 50 mg/L oxidized LDL (O); 50 mg/L oxidized LDL + 40 mg/L HDL from wild type mice (OH); 50 mg/L oxidized LDL + 40 mg/L HDL from mice (KO); or with serum-free media as controls (C). Bold italic and italic cells in the Table indicate . Bold italic indicates that the mean values are significantly higher; italic indicates significantly lower. Bold text indicates . *Results are expressed as the mean quotients of the areas under the peak of the different experimental conditions. For example, galactose values are, on average, 2.58 times higher when endothelial cells are incubated with oxidized LDL than when incubated with native LDL. All measurements were performed in triplicate.