Correlation of the change of plasma cysteinylglycine and hexadecanedioate levels with the antihypertensive effect of amlodipine.

<p>Correlation coefficients (r) and P values from partial correlation, calculated with normalized metabolite change values and controlling for metabolite baseline level, are included. dASBP, change of 24-hour ambulatory systolic blood pressure; dADBP, change of 24-hour ambulatory diastolic blood pressure.</p

Effect of antihypertensive drugs on selected plasma acylcarnitines.

<p>Plasma metabolite level is presented as relative units: the median of all analyzed samples was set to 1. Box-and-whisker plots are presented. P values <0.05 from Wilcoxon signed-rank test are included. P, placebo (mean of three periods); A, amlodipine; B, bisoprolol; H, hydrochlorothiazide; L, losartan.</p

Effect of antihypertensive drugs on selected plasma long-chain fatty acids.

<p>Plasma metabolite level is presented as relative units: the median of all analyzed samples was set to 1. Box-and-whisker plots are presented. P values <0.05 from Wilcoxon signed-rank test are included. P, placebo (mean of three periods); A, amlodipine; B, bisoprolol; H, hydrochlorothiazide; L, losartan.</p

Characteristics of the study subjects.

<p>Characteristics of the study subjects.</p

Fig 2 -

A: Schematic diagram showing the interventional clinical study design and the sample collection timeline. B: Median and interquartile range changes in the serum VEGF concentration after 4 weeks of daily monotherapies with amlodipine (5 mg), bisoprolol (5 mg), hydrochlorothiazide (25 mg) or losartan (50 mg) compared to the wash-out phases. The nonparametric Wilcoxon signed ranks test was used to test the statistical significance of the drug-induced changes in serum VEGF. *P-value < 0.05 denotes statistical significance.</p

S4 Fig -

A. MIO-M1 cells viability determination. Survival of MIO-M1 cells at end of drug treatment (96 hours), based on intracellular ATP concentration. Survival mean percentages are calculated from two independent experiments. Vertical lines represent standard deviation. B. MIO-M1 cells viability, DMSO vs 1xPBS treatment. Luminescence [quantified as Relative Light Units (RLU)] based assay to measure intracellular ATP indicating general cell health. Our data show no statistically significant difference in the intracellular ATP concentration between DMSO and 1xPBS in MIO-M1 cells; 96 hours post treatment (End of experiment). Vertical lines represent standard deviation. (TIF)</p

S2 Fig -

A. Effects on VEGF concentrations in the MIO-M1 cells after treatment with losartan. Vertical bars represent the mean and the standard deviation of fold changes in the VEGF concentrations in the MIO-M1 cell culture medium at different time points (24 hours, 48 hours, 72 hours and 96 hours) after treatment with losartan (10 μM) vs control. Fold changes are calculate by dividing a concentration at a time point by the mean control concentration of 92.04108 pg/ml. NS = Not Significant (Mann-Whitney U test). B. Effects on VEGF concentrations in the MIO-M1 cells after treatment with lisinopril. Vertical bars represent the mean and the standard deviation of fold changes in the VEGF concentrations in the MIO-M1 cell culture medium at different time points (24 hours, 48 hours, 72 hours and 96 hours) after treatment with lisinopril (10 μM) vs control. Fold changes are calculate by dividing a concentration at a time point by the mean control concentration of 100.1139 pg/ml. NS = Not Significant (Mann-Whitney U test). (TIF)</p

Dose-response determination for amlodipine concentrations and time points to measure VEGF in cell culture media.

Dose-response (1, 5 and 10 μM) pilot experiment for determination of effects of amlodipine on VEGF secretion in MIO-M1 cells and to find out an optimal experimental setting for amlodipine concentrations and time points to measure VEGF in cell culture media. Values for VEGF concentrations are calculated as mean of three technical repeats for every treatment from a single experiment. (TIF)</p

Fig 1 -

A: Schematic diagram showing the experimental setup and the sample collection timeline. B: Vertical bars represent the mean and the standard deviation of fold changes in the VEGF concentrations in the MIO-M1 cell culture medium at different time points (24 hours, 48 hours, 72 hours and 96 hours) after treatment with amlodipine (10 μM) vs control. Fold changes in the VEGF concentration are calculated by dividing the concentration at a timepoint by the mean control concentration of 125.8765 pg/ml. *P-value = 0.007937.</p

The selection criteria for observational study cohort.

Schematic diagram depicting selection criteria in the observational study with FinnDiane cohort. (TIF)</p