(HealthDay News) – The mechanism by which proton pump inhibitors (PPIs) increase the risk of major adverse cardiovascular events may now be better understood, according to a study published online July 3 in Circulation.

Yohannes T. Ghebremariam, PhD, from the Texas Methodist Hospital Research Institute in Houston, and colleagues studied human tissue and mouse models to determine how PPIs might cause cardiovascular problems.

The researchers found that PPIs elevate plasma asymmetric dimethylarginine (ADMA) levels and reduce nitric oxide (NO) levels and endothelium-dependent vasodilation. Elevated levels of plasma ADMA, an endogenous inhibitor of nitric oxide synthase (NOS), are likely associated with increased risk for cardiovascular disease due to the reduction of the vasoprotective effects of endothelial NOS. PPIs increase ADMA as they bind to and inhibit dimethylarginine dimethylaminohydrolase (DDAH), the enzyme that degrades ADMA.

“This finding compels additional clinical investigations and pharmacovigilance directed toward understanding the cardiovascular risk associated with use of the PPIs in the general population,” the authors write.

Two authors are inventors on patents owned by Stanford University that protect the use of agents that modulate the NOS/DDAH pathway therapeutically.

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