The Microbiota Promotes Arterial Thrombosis in Low-Density Lipoprotein Receptor-Deficient Mice
| Autor: | Michael Molitor, Felix Sommer, Giulia Pontarollo, Saravanan Subramaniam, Yvonne Jansen, Hristo Todorov, Kerstin Jurk, Magdolna Nagy, Yvonne Döring, Christian Weber, Marijke J.E. Kuijpers, Stefanie Ascher, Sven Jäckel, Philip Wenzel, Johan W. M. Heemskerk, Cornelia Karwot, Ulrich Walter, Klytaimnistra Kiouptsi, Christoph Reinhardt, Susanne Gerber, Eivor Wilms, Carlos Neideck, Franziska Bayer, Henning Formes, Alexandra Grill, Emiel P. C. van der Vorst, Philip Rosenstiel, Bettina Kollar |
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| Přispěvatelé: | RS: CARIM - R1.03 - Cell biochemistry of thrombosis and haemostasis, MUMC+: HVC Pieken Trombose (9), RS: Carim - B03 Cell biochemistry of thrombosis and haemostasis, RS: CARIM - R1 - Thrombosis and haemostasis, Biochemie, Promovendi CD, RS: Carim - B07 The vulnerable plaque: makers and markers, Pathologie |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0209 industrial biotechnology Very low-density lipoprotein Chemokine CXCL1 02 engineering and technology 030204 cardiovascular system & hematology arterial thrombosis Applied Microbiology and Biotechnology ACTIVATION Mice chemistry.chemical_compound 020901 industrial engineering & automation 0302 clinical medicine germfree 0202 electrical engineering electronic engineering information engineering Medicine vascular inflammation Platelet Chemokine CCL7 lcsh:QH301-705.5 platelet 0303 health sciences atherosclerosis mouse models food and beverages Thrombosis Plaque Atherosclerotic QR1-502 late atherosclerosis 3. Good health Holobiont low-density lipoprotein receptor germ-free platelets cardiovascular system Female lipids (amino acids peptides and proteins) GLYCOPROTEIN-VI Blood stream Research Article RECRUITMENT medicine.medical_specialty Nutritional composition COAGULATION 610 Medicine & health Biology METABOLISM Biochemistry Genetics and Molecular Biology (miscellaneous) Microbiology Host-Microbe Biology Proinflammatory cytokine PLATELET HYPERREACTIVITY 03 medical and health sciences INFLAMMATION Virology Internal medicine atherothrombosis Genetics microbiota Animals Interleukin 9 Platelet activation cardiovascular diseases Thrombus Molecular Biology 030304 developmental biology gut microbiota business.industry Cholesterol carotid artery 020208 electrical & electronic engineering cholesterol nutritional and metabolic diseases Cell Biology medicine.disease Microreview CHLAMYDIA-PNEUMONIAE Mice Mutant Strains Gastrointestinal Microbiome Endocrinology Receptors LDL lcsh:Biology (General) chemistry Arterial thrombus LDL receptor Parasitology atherosclerosis business Ex vivo Lipoprotein |
| Zdroj: | mBio, Vol 10, Iss 5 (2019) mBio, Vol 10, Iss 5, p e02298-19 (2019) Kiouptsi, Klytaimnistra; Jäckel, Sven; Pontarollo, Giulia; Grill, Alexandra; Kuijpers, Marijke J E; Wilms, Eivor; Weber, Christian; Sommer, Felix; Nagy, Magdolna; Neideck, Carlos; Jansen, Yvonne; Ascher, Stefanie; Formes, Henning; Karwot, Cornelia; Bayer, Franziska; Kollar, Bettina; Subramaniam, Saravanan; Molitor, Michael; Wenzel, Philip; Rosenstiel, Philip; ... (2019). The Microbiota Promotes Arterial Thrombosis in Low-Density Lipoprotein Receptor-Deficient Mice. mBio, 10(5) American Society for Microbiology 10.1128/mBio.02298-19 Microbial Cell, Vol 7, Iss 1, Pp 28-31 (2020) Mbio, 10(5):e02298-19. American Society for Microbiology mBio Microbial Cell |
| ISSN: | 2150-7511 |
| Popis: | 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. Atherosclerotic plaque development depends on chronic inflammation of the arterial wall. A dysbiotic gut microbiota can cause low-grade inflammation, and microbiota composition was linked to cardiovascular disease risk. However, the role of this environmental factor in atherothrombosis remains undefined. To analyze the impact of gut microbiota on atherothrombosis, we rederived low-density lipoprotein receptor-deficient (Ldlr−/−) mice as germfree (GF) and kept these mice for 16 weeks on an atherogenic high-fat Western diet (HFD) under GF isolator conditions and under conventionally raised specific-pathogen-free conditions (CONV-R). In spite of reduced diversity of the cecal gut microbiome, caused by atherogenic HFD, GF Ldlr−/− mice and CONV-R Ldlr−/− mice exhibited atherosclerotic lesions of comparable sizes in the common carotid artery. In contrast to HFD-fed mice, showing no difference in total cholesterol levels, CONV-R Ldlr−/− mice fed control diet (CD) had significantly reduced total plasma cholesterol, very-low-density lipoprotein (VLDL), and LDL levels compared with GF Ldlr−/− mice. Myeloid cell counts in blood as well as leukocyte adhesion to the vessel wall at the common carotid artery of GF Ldlr−/− mice on HFD were diminished compared to CONV-R Ldlr−/− controls. Plasma cytokine profiling revealed reduced levels of the proinflammatory chemokines CCL7 and CXCL1 in GF Ldlr−/− mice, whereas the T-cell-related interleukin 9 (IL-9) and IL-27 were elevated. In the atherothrombosis model of ultrasound-induced rupture of the common carotid artery plaque, thrombus area was significantly reduced in GF Ldlr−/− mice relative to CONV-R Ldlr−/− mice. Ex vivo, this atherothrombotic phenotype was explained by decreased adhesion-dependent platelet activation and thrombus growth of HFD-fed GF Ldlr−/− mice on type III collagen. |
| Databáze: | OpenAIRE |
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