Scientific Update on Endothelial Function Sponsored by Endothelix Inc.
Proton Pump Inhibitors Accelerate Endothelial Senescence
Gautham Yepuri1 , Roman Sukhovershin1 , Timo Z Nazari-Shafti1 , Michael Petrascheck2 , Yohannes T. Ghebre3 , John P. Cooke1 1 Department of Cardiovascular Sciences, Center for Cardiovascular Regeneration, Houston Methodist Research Institute, Houston, TX, USA; 2 Department of Chemical Physiology, Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA, and; 3 Department o
We find that chronic exposure of human endothelial cells to the PPIs esomeprazole or SCH-28080 accelerates endothelial aging. This adverse effect appears to be due to an inhibition of lysosomal acidification and subsequent impairment of proteostasis. The accumulation of protein aggregates is associated with an increase in oxidative stress, endothelial dysfunction and senescence. Vascular senescence would provide a mechanistic explanation11-13 for the accumulating evidence that PPIs increase the risk of cardiovascular morbidity and mortality, renal failure, and dementia.2-5
In the presence of consistent epidemiological evidence of harm, and a unifying mechanism for the disparate disorders linked to PPI use; and with the knowledge that PPIs are being used by millions of people for indications and durations that were never tested or approved; it is time for the pharmaceutical industry and regulatory agencies to re-visit the specificity and the safety of these agents.
Evaluate Endothelial Function with VENDYS Digital Thermal Monitoring of Vascular Reactivity