Author Interviews, Gastrointestinal Disease, Heart Disease / 20.08.2013
PPIs – Proton Pump Inhibitors Impair Vascular Relaxation, May Increase Adverse CV Events
MedicalResearch.com Interview with:
John P. Cooke MD PhD
Chair, Department of Cardiovascular Sciences
Director, Center for Cardiovascular Regeneration
Houston Methodist Research Institute
6670 Bertner St MS: R6-414, Houston, TX 77030
MedicalResearch.com: What are the main findings of the study?
Answer: We discovered that the proton pump inhibitors PPIs), as a class, impair vascular relaxation. The PPIs have this effect by suppressing the activity of a key enzyme required for cardiovascular health. The enzyme is known as DDAH (for dimethylarginine dimethylaminohydrolase). This enzyme is critical in clearing ADMA (asymmetric dimethylarginine) from tissues and the circulation. Because ADMA is an endogenous inhibitor of nitric oxide synthase, accumulation of ADMA impairs vascular relaxation and vascular homeostasis. Previously, we and others have found that, by inhibiting endothelium-derived nitric oxide, ADMA accelerates vascular disease in preclinical models. In humans, ADMA is linked to the severity of vascular disease, and is an independent risk factor for major adverse cardiovascular events (MACE). Thus, the effect of PPIs to inhibit DDAH would be anticipated to impair cardiovascular health, and to increase the risk of MACE.
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