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Gut microbes affect platelet function, risk for MI, stroke
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New data published in Cell from Cleveland Clinic researchers suggest that gut-derived metabolite trimethylamine N-oxide triggers over-reactive platelet function, increasing the risk for thrombosis, MI and stroke.
Gut-derived metabolite trimethylamine N-oxide (TMAO) is a byproduct of the nutrient choline found in meats and eggs. In a previous study, the researchers observed a connection between elevated TMAO and MI and stroke. Their new research, a combination of clinical studies and animal model studies, focused particularly on platelet function and risk for thrombosis.
“It is remarkable that gut microbes produce a compound that alters platelet function and thrombotic [MI] and stroke risk,” Stanley Hazen, MD, PhD, chair of the department of cellular and molecular medicine in the Lerner Research Institute and head of preventive cardiology and rehabilitation in the Miller Family Heart & Vascular Institute at Cleveland Clinic, said in a press release.
Stanley Hazen
In this study, Hazen and colleagues reanalyzed the initial data from 4,007 patients and observed a link between TMAO and thrombosis risk, even after adjusting for potential confounders such as CVD history, traditional CVD risk factors and medications (adjusted HR for highest quartile vs. lowest quartile = 1.64; P < .0001).
They then performed additional studies on human platelets and animal models to examine closer TMAO’s impact on platelet function and clotting rate.
“We have shown that TMAO fundamentally alters calcium-signaling within platelets; when TMAO is elevated, platelet responsiveness to known triggers like thrombin, collagen or [adenosine diphosphate] is heightened,” Hazen said. “In general, there’s a broad range for how quickly different people will form clots. However, across the board, when TMAO is elevated, platelet responsiveness jumps to the hyper-reactive side of normal. ... This new link helps explain how diet-induced TMAO generation is mechanistically linked to development of lethal adverse complications of heart disease.”
Overall, the findings suggested that reducing TMAO levels in the body either by diet or medical therapy may be a new strategy in the prevention of CVD. They also discovered that TMAO production and thrombosis potential are transmissible via microbial transplantation.
“The clinical utility of TMAO levels as an indication of subjects who may benefit from antiplatelet prophylaxis therapy with low-dose aspirin or other platelet-directed antithrombotic drugs” must be investigated further, the researchers wrote. – by Tracey Romero
Disclosure: Hazen reports receiving funding from the Leonard Krieger endowment. Please see full study for list of all other researchers’ relevant financial disclosures.
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