The involvement of vascular endothelial growth factor type C (VEGF-C) in the regulation of the relationship between sodium intake and blood pressure
salt sensitivity ; salt ; hypertension ; subcutaneous tissue
Objective: Vascular endothelial growth factor type C (VEGF-C) is a novel marker for sodium accumulation in the subcutaneous tissue, yet unexplored in humans. Animal studies have shown a significant correlation between excess sodium intake, increased levels of VEGF-C in the plasma and higher blood pressure. The aim of this thesis was to evaluate the relationship between the level of serum VEGF-C and blood pressure in the general population, determine the factors influencing VEGF-C serum levels in population and to assess the impact of the interaction between plasma VEGF-C and sodium intake on the blood pressure in the general population. Methods: In this cross-sectional cohort study, participants were recruited from the general population of the Malopolska Region of Poland, including 109 families, a total of 303 people. With every participant, we performed: ambulatory blood pressure measurement (SpaceLabs 90207), complete blood count, serum concentration of creatinine, uric acid, C-reactive protein, glucose, electrolytes (sodium, potassium), lipid profile, measurement of plasma renin activity, levels of inflammatory markers (interleukin-6 and myeloperoxidase) and plasma VEGF-C concentration was measured using ELISA kit. Sodium intake and lithium clearance was assessed based on 24-hour urinary sodium excretion. The measurement of the extracellular fluid volume, total body water a ; nd fat mass was conducted using the method of bioelectrical impedance (Bodystat® Quadscan 4000, Isle of Man, British Isles). Statistical analyses were performed using SAS (SAS Institute, Cary, NC) version 9.3. ; Results: The study group consisted of 138 parents (57 men, 81 women) and 165 descendants (79 men, 86 women). Average age of parents was 61.5 ± 7.9 years, and of descendants 34.8 ± 8.4 years. There were no significant differences between the groups in the values of blood pressure on ambulatory monitoring, except for the daytime diastolic blood pressure that was lower in parents (75.4 ± 7.7 vs 77.4 ± 8.2 mm Hg, p <0, 05). Mean urinary sodium excretion in parents was 175 ± 71 mmol / d, and the descendants’ group 161 ± 65 mmol / d and was not significantly different. No difference was found between serum VEGF-C levels, nor between generations neither genders. Multivariate regression analyse were adjusted for age, gender, body mass index, use of antihypertensive drugs, declared smoking and alcohol consumption. In whole study group there was no association between serum VEGF-C and blood pressure throughout 24 hours, daytime and nighttime. In subgroup analysis of participants never treated with antihypertensive medications there was observed a negative correlation between serum VEGF-C and systolic (β [Beta - regression coefficient] -0.0017, p=0.047) and diastolic (β -0.0014, p ; =0.049) blood pressure over 24 hours. Such relation was not shown for the population receiving antihypertensives. In the study population, there was no significant difference in the concentration of VEGF-C levels between individuals with hypertension and normotensives. In univariate analysis there was demonstrated a significant, positive correlation between the concentration of serum VEGF-C and the extracellular fluid volume (r = 0.1897 p 0.0047) as well as plasma concentration of aldosterone (r 0.1406 p=0.0148). This correlation was more pronounced in the subgroup of patients not treated with antihypertensives (r 0.23623 p=0.003 and r 0.0148, p=0.0015). Using stepwise regression analysis as the determinants of plasma VEGF-C levels there were selected: extracellular fluid volume (r2 0.038, p=0.0047), plasma aldosterone levels (r2 0.0635 p=0.0123) and plasma levels of myeloperoxidase (r2 0.0752 p=0.0996). The proposed model explained 7.5% of the observed variability in concentrations of VEGF-C. In the study group, we did not observed any interaction between serum VEGF-C, sodium excretion and blood pressure throughout 24 hours, daytime and nighttime. While analysing subgroup of participants never treated with antihypertensive medications we observed negative interaction between concentration of VEGF-C and excretion of sodium and night-time diastolic blood pressure (β -0.0014, p=0 ; .049). ; Conclusions: In the whole group in the multivariate analysis, there was no association between serum VEGF-C levels and blood pressure. In the subgroup of subjects never treated with antihypertensive medications we demonstrated a negative correlation between serum VEGF-C levels and systolic and diastolic blood pressure over 24 hours period. This indicates that the subcutaneous sodium buffer participates in the regulation of blood pressure.In our population higher concentration of VEGF-C levels were associated with a higher percentage of extracellular fluid in the body, and a higher plasma concentration of aldosterone but with a lower plasma concentration of myeloperoxidase. This points to the existence of links between the production of VEGF-C, sodium homeostasis and the mechanisms of the immune response.We showed an interaction between sodium intake and the concentration of VEGF-C levels in relation to diastolic blood pressure at night, which may indicate their overall importance in the regulation of circadian blood pressure profile.