Lifelong dietary omega-3 fatty acid suppresses thrombotic potential through gut microbiota alteration in aged mice
Seyed Soheil Saeedi Saravi,
Nicole R. Bonetti,
Benoit Pugin,
Florentin Constancias,
Lisa Pasterk,
Sara Gobbato,
Alexander Akhmedov,
Luca Liberale,
Thomas F. Lüscher,
Giovanni G. Camici,
Jürg H. Beer
Affiliations
Seyed Soheil Saeedi Saravi
Laboratory for Platelet Research, Center for Molecular Cardiology, University of Zurich, 8952 Schlieren, Switzerland; Department of Internal Medicine, Cantonal Hospital Baden, Im Ergel 1, 5404 Baden, Switzerland
Nicole R. Bonetti
Laboratory for Platelet Research, Center for Molecular Cardiology, University of Zurich, 8952 Schlieren, Switzerland; Department of Internal Medicine, Cantonal Hospital Baden, Im Ergel 1, 5404 Baden, Switzerland
Benoit Pugin
Laboratory of Food Biotechnology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland
Florentin Constancias
Laboratory of Food Biotechnology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland
Lisa Pasterk
Laboratory for Platelet Research, Center for Molecular Cardiology, University of Zurich, 8952 Schlieren, Switzerland
Sara Gobbato
Department of Internal Medicine, Cantonal Hospital Baden, Im Ergel 1, 5404 Baden, Switzerland
Alexander Akhmedov
Center for Molecular Cardiology, University of Zurich, 8952 Schlieren, Switzerland
Luca Liberale
Center for Molecular Cardiology, University of Zurich, 8952 Schlieren, Switzerland; Department of Internal Medicine, University of Genoa, Genoa, Italy
Thomas F. Lüscher
Center for Molecular Cardiology, University of Zurich, 8952 Schlieren, Switzerland; Royal Brompton and Harefield Hospitals and Imperial College, London, UK
Giovanni G. Camici
Center for Molecular Cardiology, University of Zurich, 8952 Schlieren, Switzerland; University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland; Department of Research and Education, University Hospital Zurich, Zurich, Switzerland
Jürg H. Beer
Laboratory for Platelet Research, Center for Molecular Cardiology, University of Zurich, 8952 Schlieren, Switzerland; Department of Internal Medicine, Cantonal Hospital Baden, Im Ergel 1, 5404 Baden, Switzerland; Corresponding author
Summary: Aging is a major risk factor for cardiovascular diseases, including thrombotic events. The gut microbiota has been implicated in the development of thrombotic risk. Plant-derived omega-3 fatty acid ɑ-linolenic acid (ALA) confers beneficial anti-platelet and anti-inflammatory effects. Hence, antithrombotic activity elicited by ALA may be partly dependent on its interaction with gut microbiota during aging. Here, we demonstrate that lifelong dietary ALA decreases platelet hyperresponsiveness and thrombus formation in aged mice. These phenotypic changes can be partly attributed to alteration of microbial composition and reduction of its metabolite trimethylamine N-oxide and inflammatory mediators including TNF-α, as well as the upregulated production of short-chain fatty acid acetate. ALA-rich diet also dampens secretion of increased procoagulant factors, tissue factor and plasminogen activator inhibitor-1, in aged mice. Our results suggest long-term ALA supplementation as an attractive, accessible, and well-tolerated nutritional strategy against age-associated platelet hyperreactivity and thrombotic potential.
