0000000000349848
AUTHOR
Alexandra Grill
The Gut Microbiota in Cardiovascular Disease and Arterial Thrombosis
The gut microbiota has emerged as a contributing factor in the development of atherosclerosis and arterial thrombosis. Metabolites from the gut microbiota, such as trimethylamine N-oxide and short chain fatty acids, were identified as messengers that induce cell type-specific signaling mechanisms and immune reactions in the host vasculature, impacting the development of cardiovascular diseases. In addition, microbial-associated molecular patterns drive atherogenesis and the microbiota was recently demonstrated to promote arterial thrombosis through Toll-like receptor signaling. Furthermore, by the use of germ-free mouse models, the presence of a gut microbiota was shown to influence the syn…
Evaluation of blood collection methods and anticoagulants for platelet function analyses on C57BL/6J laboratory mice
The exploration of thrombotic mechanisms relies on the application of blood collection methods from laboratory mice with a minimal pre-activation of platelets and the clotting system. So far, very little is known on how the blood collection method and the anticoagulant used influence pre-activation of mouse platelets and coagulation. To determine the most suitable blood collection method, we systematically compared blood collection by heart puncture,
The Microbiota Promotes Arterial Thrombosis in Low-Density Lipoprotein Receptor-Deficient Mice
Our results demonstrate a functional role for the commensal microbiota in atherothrombosis. In a ferric chloride injury model of the carotid artery, GF C57BL/6J mice had increased occlusion times compared to colonized controls. Interestingly, in late atherosclerosis, HFD-fed GF Ldlr−/− mice had reduced plaque rupture-induced thrombus growth in the carotid artery and diminished ex vivo thrombus formation under arterial flow conditions.
Specialized regulatory T cells control venous blood clot resolution through SPARC.
Abstract The cells and mechanisms involved in blood clot resorption are only partially known. We show that regulatory T cells (Tregs) accumulate in venous blood clots and regulate thrombolysis by controlling the recruitment, differentiation and matrix metalloproteinase (MMP) activity of monocytes. We describe a clot Treg population that forms the matricellular acid– and cysteine-rich protein SPARC (secreted protein acidic and rich in cysteine) and show that SPARC enhances monocyte MMP activity and that SPARC+ Tregs are crucial for blood clot resorption. By comparing different treatment times, we define a therapeutic window of Treg expansion that accelerates clot resorption.
Gut Microbiota Restricts NETosis in Acute Mesenteric Ischemia-Reperfusion Injury.
Objective: Recruitment of neutrophils and formation of neutrophil extracellular traps (NETs) contribute to lethality in acute mesenteric infarction. To study the impact of the gut microbiota in acute mesenteric infarction, we used gnotobiotic mouse models to investigate whether gut commensals prime the reactivity of neutrophils towards formation of neutrophil extracellular traps (NETosis). Approach and Results: We applied a mesenteric ischemia-reperfusion (I/R) injury model to germ-free (GF) and colonized C57BL/6J mice. By intravital imaging, we quantified leukocyte adherence and NET formation in I/R-injured mesenteric venules. Colonization with gut microbiota or monocolonization with Esch…
IL-17 controls central nervous system autoimmunity through the intestinal microbiome
Interleukin-17A- (IL-17A) and IL-17F-producing CD4(+) T helper cells (T(H)17 cells) are implicated in the development of chronic inflammatory diseases, such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). T-H 17 cells also orchestrate leukocyte invasion of the central nervous system (CNS) and subsequent tissue damage. However, the role of IL-17A and IL-17F as effector cytokines is still confused with the encephalitogenic function of the cells that produce these cytokines, namely, T-H 17 cells, fueling a long-standing debate in the neuroimmunology field. Here, we demonstrated that mice deficient for IL-17A/F lose their susceptibility to EAE, which…
Endothelial GLP-1 (Glucagon-Like Peptide 1) Receptor Mediates Cardiovascular Protection by Liraglutide In Mice With Experimental Arterial Hypertension
Supplemental Digital Content is available in the text.
Aestivation motifs explain hypertension and muscle mass loss in mice with psoriatic skin barrier defect
Aim Recent evidence suggests that arterial hypertension could be alternatively explained as a physiological adaptation response to water shortage, termed aestivation, which relies on complex multi-organ metabolic adjustments to prevent dehydration. Here, we tested the hypothesis that chronic water loss across diseased skin leads to similar adaptive water conservation responses as observed in experimental renal failure or high salt diet. Methods We studied mice with keratinocyte-specific overexpression of IL-17A which develop severe psoriasis-like skin disease. We measured transepidermal water loss and solute and water excretion in the urine. We quantified glomerular filtration rate (GFR) by…