Proton Pump Inhibitors Accelerate Endothelial Senescence

Abstract

Rationale Proton pump inhibitors (PPIs) are popular drugs for gastroesophageal reflux, now available for long-term use without medical supervision. Recent reports suggest that PPI use is associated with cardiovascular, renal and neurological morbidity. Objective To study the long-term effect of PPIs on endothelial dysfunction and senescence and investigate the mechanism involved in PPI induced vascular dysfunction. Methods and Results Chronic exposure to PPIs impaired endothelial function and accelerated human endothelial senescence by reducing telomere length. Conclusion Our data may provide a unifying mechanism for the association of PPI use with increased risk of cardiovascular, renal and neurological morbidity and mortality.

Gastroprotection with proton-pump inhibitors in high-risk cardiovascular patients: who to target and for how long?

“…However, a subsequent study by the same authors in healthy volunteers and patients with CAD failed to validate this posited mechanism [6]. More recently, Yepuri et al reported that PPIs may accelerate senescence in human endothelial lysosomes by curtailing telomere length [7]; however, this mechanism requires further study.…”

Letter by Marlicz et al Regarding Article, “Proton Pump Inhibitors Accelerate Endothelial Senescence”

“…We read with great interest the study by Yepuri et al 1 on the effects of proton pump inhibitors (PPIs) on endothelial cells. The investigators exposed human microvascular endothelial cells to PPIs and observed reduced cell proliferation, a decrease in NO, and impaired proteostasis.…”

Does the Existence of Senolytic Compounds Underpin that Anti-Senolytics May Exist? A view on the Heaven and Hell of Cellular Senescence

“…However, there are several other compounds which display side effects likely associated toinduction of senescence. Very recently, accelerated endothelial senescence has been claimed as a potential mechanism to explain the cardiovascular, renal and neurological morbidity associated with proton pump inhibitors use [17]. The poor knowledge around effects on normal cells and potential side effects of senoltyics also deserve particular care.…”