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Description:
Commensal microbiota are increasingly recognized participants in cardiometabolic diseases and central modulators of immunity, allergies and autoimmunity. The symbiotic relationship of the microbiome with epithelial interfaces crucially depends on an interplay of microbiota-derived metabolites, host innate immune sensing, and regulation of adaptive immunity. These local interactions particularly in the intestinal milieu have profound effects on the vasculature and contribute to thrombosis through a steadily expanding repertoire of recognized molecular mechanisms. This session will highlight recent cutting-edge research deciphering pathways by which microbiota influence the vascular endothelium and touch in this context on cerebral vascular disease and autoimmunity-evoked thrombosis.
Dr. Martin Kriegel will discuss the role of the microbiota in thrombosis with a focus on the antiphospholipid syndrome. He will provide an overview of the pathogenesis and the importance of ?2-glycoprotein I in thrombosis and of pathobionts within the human gut microbiota that elicit antibodies cross-reactive with epitopes of ?2-glycoprotein I. Dr. Kriegel will link the cross-reactive process with pathogenic autoantibodies leading to thrombosis in an animal model in vivo as well as trophoblast dysfunction in vitro.
Dr. Mark Kahn will present the identification of a gut-brain disease axis for vascular malformation and implications for novel treatment strategies. Loss of function in the genes encoding cerebral cavernous malformation (CCM) adaptor proteins in endothelial cells causes vascular formations that form in the brain and are a significant cause for stroke and seizure in younger individuals. CCM loss of function results in gain of signaling by the MEKK3-KLF2/4 pathway. Unexpectedly, a major input to this pathway in brain endothelial cells is the TLR4 innate immune receptor, the activity of which is strongly influenced by the gut microbiome and gut epithelial barrier function.
Dr. Weifei Zhu has examined the role of gut microbes in modulating stroke susceptibility and functional recovery post stroke onset. Over the past few years, mechanistic links have been developed between nutrients in a western diet, gut microbiota formation of the metabolite trimethylamine N oxide (TMAO), and the development of both platelet hyper-responsiveness and cardiovascular diseases. Dr. Zhu will address the meta-organismal TMAO pathway as a stroke risk factor, depict potential mechanisms contributing to diet enhanced ischemic stroke risks, and explore novel therapeutic approaches targeting gut microbial contributions for prevention and treatment in cerebrovascular disease.
Dr. Martin Kriegel will discuss the role of the microbiota in thrombosis with a focus on the antiphospholipid syndrome. He will provide an overview of the pathogenesis and the importance of ?2-glycoprotein I in thrombosis and of pathobionts within the human gut microbiota that elicit antibodies cross-reactive with epitopes of ?2-glycoprotein I. Dr. Kriegel will link the cross-reactive process with pathogenic autoantibodies leading to thrombosis in an animal model in vivo as well as trophoblast dysfunction in vitro.
Dr. Mark Kahn will present the identification of a gut-brain disease axis for vascular malformation and implications for novel treatment strategies. Loss of function in the genes encoding cerebral cavernous malformation (CCM) adaptor proteins in endothelial cells causes vascular formations that form in the brain and are a significant cause for stroke and seizure in younger individuals. CCM loss of function results in gain of signaling by the MEKK3-KLF2/4 pathway. Unexpectedly, a major input to this pathway in brain endothelial cells is the TLR4 innate immune receptor, the activity of which is strongly influenced by the gut microbiome and gut epithelial barrier function.
Dr. Weifei Zhu has examined the role of gut microbes in modulating stroke susceptibility and functional recovery post stroke onset. Over the past few years, mechanistic links have been developed between nutrients in a western diet, gut microbiota formation of the metabolite trimethylamine N oxide (TMAO), and the development of both platelet hyper-responsiveness and cardiovascular diseases. Dr. Zhu will address the meta-organismal TMAO pathway as a stroke risk factor, depict potential mechanisms contributing to diet enhanced ischemic stroke risks, and explore novel therapeutic approaches targeting gut microbial contributions for prevention and treatment in cerebrovascular disease.