Gautham Yepuri1, Roman Sukhovershin1, Timo Z Nazari-Shafti1, Michael Petrascheck1, Yohannes T Ghebre1, John P Cooke2. 1. From the Department of Cardiovascular Sciences, Center for Cardiovascular Regeneration, Houston Methodist Research Institute, TX (G.Y., R.S., T.Z.N-.S., J.P.C.); Department of Chemical Physiology, Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA (M.P.); and Department of Radiation Oncology, Baylor College of Medicine, One Baylor Plaza, Houston, TX (Y.T.G.). 2. From the Department of Cardiovascular Sciences, Center for Cardiovascular Regeneration, Houston Methodist Research Institute, TX (G.Y., R.S., T.Z.N-.S., J.P.C.); Department of Chemical Physiology, Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA (M.P.); and Department of Radiation Oncology, Baylor College of Medicine, One Baylor Plaza, Houston, TX (Y.T.G.). jpcooke@houstonmethodist.org.
Abstract
RATIONALE: Proton pump inhibitors (PPIs) are popular drugs for gastroesophageal reflux, which are 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. CONCLUSIONS: Our data may provide a unifying mechanism for the association of PPI use with increased risk of cardiovascular, renal, and neurological morbidity and mortality.
RATIONALE: Proton pump inhibitors (PPIs) are popular drugs for gastroesophageal reflux, which are 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. CONCLUSIONS: Our data may provide a unifying mechanism for the association of PPI use with increased risk of cardiovascular, renal, and neurological morbidity and mortality.
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