Recent studies on biological activity of ANG have extended their function from enabling cell growth and proliferation to sustaining endothelial cell survival under various stresses including heat shock, hypothermia, hypoxia, and radiation [ 26- 30].
Several articles report the potential effect of insulin as a key factor to sustain human endothelial function via its capacity to stimulate synthesis of nitric oxide and uptake and metabolism of amino acids and other substrates [ 5].
Hypertension, hypercholesterolemia, diabetes, and aging, which may all be associated with an excessive production of reactive oxygen species (ROS) and oxidant stress, may contribute to atherosclerosis by affecting endothelial function and inducing sustained endothelial activation [ 2- 5].
Figure 5: Sustained endothelial Wnt/β-catenin signaling and heart failure.
It was also shown that conditioned medium from heparanase-overexpressing cells sustain endothelial cell proliferation.
It was demonstrated that short-term (72 hours) and short-term intermittent (for five hours, biweekly) administration of dobutamine has a sustained beneficial effect on vascular endothelial function for two weeks or longer and after four months, respectively [ 25, 26].
A study by Ip et al demonstrated that the FMD was significantly improved after 4 weeks of CPAP treatment, while Bayram et al revealed that the improvement in the endothelial function was sustained after 6 months of treatment in complaint patients.
These rapid structural changes were accompanied by early improvements in arterial stiffness and endothelial function that were sustained to 12 months.
Longer trials are required to establish if the higher levels of walnut consumption associated with improved lipid profiles or endothelial function can be sustained over time and reduce clinical end-points.
Therefore, we believe that the improved endothelial function with sustained walnut consumption that we observed would be sustained in conditions approximating a real-world setting.
A further study has shown that fluctuating glucose levels have a stronger effect on endothelial function (important in the pathogenesis of preeclampsia [ 14]) than sustained hyperglycemia (15).
