Microbiota are critical for vascular physiology: Germ-free status weakens contractility and induces sex-specific vascular remodeling in mice

Vascul Pharmacol. Feb-Mar 2020;125-126:106633. doi: 10.1016/j.vph.2019.106633. Epub 2019 Dec 13.

Abstract

Commensal microbiota within a holobiont contribute to the overall health of the host via mutualistic symbiosis. Disturbances in such symbiosis is prominently correlated with a variety of diseases affecting the modern society of humans including cardiovascular diseases, which are the number one contributors to human mortality. Given that a hallmark of all cardiovascular diseases is changes in vascular function, we hypothesized that depleting microbiota from a holobiont would induce vascular dysfunction. To test this hypothesis, young mice of both sexes raised in germ-free conditions were examined vascular contractility and structure. Here we observed that male and female germ-free mice presented a decrease in contraction of resistance arteries. These changes were more pronounced in germ-free males than in germ-free females mice. Furthermore, there was a distinct change in vascular remodeling between males and females germ-free mice. Resistance arteries from male germ-free mice demonstrated increased vascular stiffness, as shown by the leftward shift in the stress-strain curve and inward hypotrophic remodeling, a characteristic of chronic reduction in blood flow. On the other hand, resistance arteries from germ-free female mice were similar in the stress-strain curves to that of conventionally raised mice, but were distinctly different and showed outward hypertrophic remodeling, a characteristic seen in aging. Interestingly, we observed that reactive oxygen species (ROS) generation from bone marrow derived neutrophils is blunted in female germ-free mice, but it is exacerbated in male germ-free mice. In conclusion, these observations indicate that commensal microbiota of a holobiont are central to maintain proper vascular function and structure homeostasis, especially in males.

Keywords: Germ-free mice; Sex differences; Vascular contractility.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bacteria / metabolism*
  • Elastic Modulus
  • Female
  • Gastrointestinal Microbiome / physiology*
  • Germ-Free Life
  • Host Microbial Interactions
  • Male
  • Mesenteric Arteries / metabolism
  • Mesenteric Arteries / physiology*
  • Mice, Inbred C57BL
  • Neutrophils / metabolism
  • Reactive Oxygen Species / metabolism
  • Sex Factors
  • Vascular Remodeling*
  • Vascular Resistance
  • Vascular Stiffness
  • Vasoconstriction*

Substances

  • Reactive Oxygen Species