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Chronic Use of Acid Reflux Drug Linked to Accelerated Vascular Aging

By Drug Discovery Trends Editor | May 11, 2016

This image shows protein aggregation in endothelial cells not exposed to PPIs. Credit: Houston MethodistLong-term exposure to common, acid reflux drugs known as proton pump inhibitors (PPI) could speed up the aging of blood vessels, according to a new study published in Circulation Research.

The research, conducted by a Houston Methodist Research Institute (HMRI) team, supports recent evidence linking long-term PPI use to increased risk of cardiovascular disease, vascular dementia and renal failure.

PPIs, like Nexium (esomeprazole), are over-the-counter medications used to reduce acid build-up in the stomach, and are often used to treat gastroesophageal reflux disease (GERD), a digestive disorder. PPIs are not approved for long-term use.

When researchers exposed human endothelial cells, which line the inside of blood vessels, to PPIs they observed accelerated biological aging of the cells. Yet, when the cells were dosed with PPIs for only a few weeks, no adverse effects were seen in the health of endothelial cells.

“The PPIs also reduce acidity in lysosomes of the endothelial cell. The lysosomes are like cellular garbage disposals and need acid to work properly,” said John Cooke, M.D., Ph.D., of HMRI. “We observed cellular garbage accumulating in the endothelial cells, which sped up the aging process.”

About 1 in 14 Americans have used PPIs, according to the U.S. Food and Drug Administration. Cooke stressed the importance of follow-up studies in a broad patient population to assess the long-term impact of PPIs on vascular health.

“With the knowledge that PPIs are being used by millions of people for indications and durations that were never tested or approved, it may be time for the pharmaceutical industry and regulatory agencies to revisit the specificity and safety of these agents,” Cooke said.

The current study does have limitations, however. Only one PPI tested is commercially available. The study was also done in a laboratory setting, and not yet in clinical trials.


Filed Under: Drug Discovery

 

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