Public Release: 

Heartburn drug damages blood vessel cells in lab finding

American Heart Association Rapid Access Journal Report

American Heart Association

DALLAS, May 10, 2016 -- A popular over-the-counter medication for heartburn, caused laboratory blood vessel cells to age quicker, according to new research in Circulation Research, an American Heart Association journal.

Reflux, often called heartburn, occurs when stomach acid backs up into the esophagus, causing irritation and damage. Mild reflux is fairly common, but frequent, severe occurrences, known as GERD for gastroesophageal reflux disease, can cause significant discomfort and may require treatment. Many people find relief by using over-the-counter medications called proton pump inhibitors (PPIs), which reduce acid produced by the stomach. In fact, the U.S. Food and Drug Administration estimates that 1 in 14 Americans have used PPIs.

After recent evidence linking long-term PPI use to several serious illnesses, including heart disease, kidney disease and dementia, researcher sought to identify how PPIs increase risk by studying their effects on blood vessel cells.

Now, researchers at Houston Methodist Research Institute (HMRI) say they have discovered that long term exposure to PPIs "accelerated biological aging in human endothelial cells which line the inside of blood vessels. When healthy, human endothelial cells create a Teflon-like coating that prevents blood from sticking. When older and diseased, the endothelium becomes more like Velcro, with blood elements sticking to the vessel to form blockages."

They also found that long-term PPI exposure impairs acid production by the lysosomes in the cells lining the blood vessel walls. They noted that the lysosome -- the part of the cell that typically clears waste products -- did not produce enough acid to clear waste. In turn, the buildup of waste caused the cell to age rapidly. Notably, another type of antacid known as an H2 antagonist, did not have this adverse effect.

"Lysosomes are like the garbage disposal of cells," said John P. Cooke, M.D., Ph.D., study lead author and professor and chair of the Department of Cardiovascular Sciences at the HMRI and director of the Houston Methodist Research Institute Center for Cardiovascular Regeneration in Texas. "They need to generate acid to get rid of cellular rubbish, and when cellular rubbish accumulates the cells age faster."

Although PPIs can be effective for short-term use, they are not meant for extended treatment, researchers said. PPIs do not require a prescription or doctor's supervision, which can lead to overuse.

"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 re-visit the specificity and the safety of these agents," Cooke said. "Unless otherwise indicated, physicians should consider PPIs only for short-term use for relief of symptoms of GERD, since we now have a 'smoking gun' that helps explain the consistent observational evidence of increased risk."

Cooke added that there are other approaches to long-term treatment that might be considered for GERD including H2 antagonists, lifestyle modifications, and in severe cases, surgical approaches.

The current one has several limitations. Although two different PPIs were tested, only one of these esomeprazole (brand name Nexium) is commercially available. In addition, it did not show how PPIs actually impair the lysosome's ability to produce enough acid to clear waste. Finally, since this study was in a laboratory setting, it could not show whether PPIs act in the same way within the human body, and long-term clinical trials are necessary.


Co-authors are Gautham Yepuri, Ph.D.; Roman Sukhovershin, Ph.D.; Timo Z. Nazari-Shafti, M.D.; Michael Petrascheck, Ph.D. and Yohannes T. Ghebre, Ph.D. Author disclosures are on the manuscript.

The National Institute of Health and the Swiss National Science Foundation funded the study.

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Researcher photo, medication images, and heart graphic are located in the right column of this release link

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