Germ-free housing conditions do not affect aortic root and aortic arch lesion size of late atherosclerotic low-density lipoprotein receptor-deficient mice

Gut Microbes. 2020 Nov 1;11(6):1809-1823. doi: 10.1080/19490976.2020.1767463. Epub 2020 Jun 24.

Abstract

The microbiota has been linked to the development of atherosclerosis, but the functional impact of these resident bacteria on the lesion size and cellular composition of atherosclerotic plaques in the aorta has never been experimentally addressed with the germ-free low-density lipoprotein receptor-deficient (Ldlr-/- ) mouse atherosclerosis model. Here, we report that 16 weeks of high-fat diet (HFD) feeding of hypercholesterolemic Ldlr-/- mice at germ-free (GF) housing conditions did not impact relative aortic root plaque size, macrophage content, and necrotic core area. Likewise, we did not find changes in the relative aortic arch lesion size. However, late atherosclerotic GF Ldlr-/- mice had altered inflammatory plasma protein markers and reduced smooth muscle cell content in their atherosclerotic root plaques relative to CONV-R Ldlr-/- mice. Neither absolute nor relative aortic root or aortic arch plaque size correlated with age. Our analyses on GF Ldlr-/- mice did not reveal a significant contribution of the microbiota in late aortic atherosclerosis.

Keywords: Microbiota; age; aortic arch; aortic root; atherosclerosis; germ-free; inflammatory markers; lesion size; low-density lipoprotein receptor-deficient mouse; macrophages; smooth muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / metabolism
  • Aorta, Thoracic / pathology*
  • Disease Models, Animal
  • Female
  • Germ-Free Life
  • Housing, Animal
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microbiota
  • Plaque, Atherosclerotic / genetics
  • Plaque, Atherosclerotic / metabolism
  • Plaque, Atherosclerotic / microbiology
  • Plaque, Atherosclerotic / pathology*
  • Receptors, LDL / deficiency
  • Receptors, LDL / genetics*

Substances

  • Receptors, LDL

Grants and funding

The project was funded by the CTH Junior Group Translational Research in Thrombosis and Hemostasis (BMBF 01EO1003 and 01EO1503), by the German Center for Cardiovascular Research (DZHK, Pillar B Project, FKZ 81 × 2210106 to C.R., Y.D., and C.W.), by a project grant from the Boehringer Ingelheim Foundation (Consortium Grant “Novel and neglected cardiovascular risk factors”) to C.R. and WR, by a project grant from the Naturwissenschaftlich-Medizinisches Forschungszentrum (NMFZ) to C.R., by the European Research Council (ERC AdG °692511) to C.W. Supported by a grant from the Interdisciplinary Center for Clinical Research within the faculty of Medicine at the RWTH Aachen University, and NWO-ZonMw Veni (91619053) to E.P.C.v.d.V. S.J., Y.D., and C.R. are members of Young DZHK. W.R. is PI of the DZHK. The work of G.P. was supported by an EMBO Short Term Fellowship (No. 7605) and by an intramural Stufe1 project grant (Inneruniversitäre Forschungsförderung).