Microbiota are critical for vascular physiology: Germ-free status weakens contractility and induces sex-specific vascular remodeling in mice.
Animals
Bacteria
/ metabolism
Elastic Modulus
Female
Gastrointestinal Microbiome
/ physiology
Germ-Free Life
Host Microbial Interactions
Male
Mesenteric Arteries
/ metabolism
Mice, Inbred C57BL
Neutrophils
/ metabolism
Reactive Oxygen Species
/ metabolism
Sex Factors
Vascular Remodeling
Vascular Resistance
Vascular Stiffness
Vasoconstriction
Germ-free mice
Sex differences
Vascular contractility
Journal
Vascular pharmacology
ISSN: 1879-3649
Titre abrégé: Vascul Pharmacol
Pays: United States
ID NLM: 101130615
Informations de publication
Date de publication:
Historique:
received:
23
09
2019
revised:
25
11
2019
accepted:
10
12
2019
pubmed:
18
12
2019
medline:
21
10
2020
entrez:
18
12
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31843471
pii: S1537-1891(19)30279-4
doi: 10.1016/j.vph.2019.106633
pmc: PMC7036036
mid: NIHMS1064728
pii:
doi:
Substances chimiques
Reactive Oxygen Species
0
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
106633Subventions
Organisme : NIGMS NIH HHS
ID : R00 GM118885
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL143082
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA219144
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest None declared.
Références
Cell. 2018 Oct 18;175(3):679-694.e22
pubmed: 30340040
Physiol Genomics. 2015 Jun;47(6):187-97
pubmed: 25829393
J Physiol. 2015 Jun 15;593(12):2547-9
pubmed: 26095019
Hypertension. 1996 Sep;28(3):505-6
pubmed: 8794840
Science. 2013 Mar 1;339(6123):1084-8
pubmed: 23328391
Med Biol Eng Comput. 2008 May;46(5):461-7
pubmed: 18228071
Blood Vessels. 1990;27(2-5):246-57
pubmed: 2242445
Circ Res. 2017 Jan 20;120(2):312-323
pubmed: 27799253
Physiol Genomics. 2018 Oct 1;50(10):837-845
pubmed: 30095376
Clin Sci (Lond). 2018 Mar 30;132(6):701-718
pubmed: 29507058
Cell. 2016 Jan 28;164(3):337-40
pubmed: 26824647
J Exp Med. 1971 Oct 1;134(4):846-56
pubmed: 4329047
Cardiovasc Res. 2008 May 1;78(2):274-85
pubmed: 18250145
Science. 2013 Sep 6;341(6150):1241214
pubmed: 24009397
Nature. 2017 Nov 30;551(7682):585-589
pubmed: 29143823
J Am Heart Assoc. 2018 Feb 16;7(4):
pubmed: 29453308
Pharmacol Res. 2019 Mar;141:276-290
pubmed: 30639374
Nat Rev Cardiol. 2019 Mar;16(3):137-154
pubmed: 30410105
Infect Immun. 1971 Feb;3(2):342-9
pubmed: 16557975
Circ Res. 2017 Jan 20;120(2):249-251
pubmed: 28104760
Am J Hypertens. 2018 Sep 11;31(10):1067-1078
pubmed: 29788246
Cell Metab. 2015 Dec 1;22(6):983-96
pubmed: 26525535
J Gerontol A Biol Sci Med Sci. 2007 Jul;62(7):696-706
pubmed: 17634315
Symbiosis. 1991;11:93-101
pubmed: 11538111
Am J Physiol. 1959 Dec;197:1345-6
pubmed: 13846013
Eur J Nutr. 2002 Nov;41 Suppl 1:I32-7
pubmed: 12420114
J Hypertens. 2014 Mar;32(3):542-54
pubmed: 24309491
Am J Physiol Regul Integr Comp Physiol. 2006 Feb;290(2):R341-4
pubmed: 16166211
Mol Psychiatry. 2013 Jun;18(6):666-73
pubmed: 22688187
Front Cell Infect Microbiol. 2017 Aug 25;7:373
pubmed: 28890882
Curr Hypertens Rep. 2017 Apr;19(4):35
pubmed: 28365886
Neurogastroenterol Motil. 2014 Jun;26(6):745-8
pubmed: 24860967
J Am Heart Assoc. 2016 Aug 30;5(9):
pubmed: 27577581
Acta Physiol (Oxf). 2014 Feb;210(2):307-16
pubmed: 24268043
Kidney Int. 2016 Dec;90(6):1191-1198
pubmed: 27575555
Exp Physiol. 2016 Feb;101(2):230-42
pubmed: 26663420
Hypertension. 2018 Jul;72(1):59-60
pubmed: 29844150
Adv Physiol Educ. 2003 Dec;27(1-4):201-6
pubmed: 14627618
Physiol Rev. 2017 Oct 1;97(4):1469-1528
pubmed: 28931564
Am J Physiol. 1997 Oct;273(4):H1699-706
pubmed: 9362233
Hypertension. 2019 Jul;74(1):184-193
pubmed: 31154901
Circ Res. 1977 Jul;41(1):19-26
pubmed: 862138
Cell Rep. 2018 Oct 16;25(3):677-689.e4
pubmed: 30332647
PLoS Biol. 2016 Aug 19;14(8):e1002533
pubmed: 27541692
J Hypertens. 2001 May;19(5):921-30
pubmed: 11393676
Cell Metab. 2019 Feb 5;29(2):362-382.e8
pubmed: 30344015
Hypertension. 2018 Nov;72(5):1125-1132
pubmed: 30354811
Curr Med Chem. 2012;19(10):1519-29
pubmed: 22360484
Physiology (Bethesda). 2017 May;32(3):224-233
pubmed: 28404738