Artery-Associated Sympathetic Innervation Drives Rhythmic Vascular Inflammation of Arteries and Veins.
Animals
Arteries
/ immunology
Cell Adhesion
Cells, Cultured
Circadian Clocks
Endothelium, Vascular
/ metabolism
Gene Expression Regulation
Humans
Inflammation
/ immunology
Intravital Microscopy
Leukocytes
/ physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Periodicity
Receptors, Adrenergic, beta-2
/ metabolism
Sympathetic Nervous System
Thrombosis
/ physiopathology
Tumor Necrosis Factor-alpha
/ metabolism
Veins
/ immunology
cell adhesion molecules
circadian rhythm
sympathetic nervous system
thrombosis
Journal
Circulation
ISSN: 1524-4539
Titre abrégé: Circulation
Pays: United States
ID NLM: 0147763
Informations de publication
Date de publication:
24 09 2019
24 09 2019
Historique:
pubmed:
14
8
2019
medline:
18
6
2020
entrez:
13
8
2019
Statut:
ppublish
Résumé
The incidence of acute cardiovascular complications is highly time-of-day dependent. However, the mechanisms driving rhythmicity of ischemic vascular events are unknown. Although enhanced numbers of leukocytes have been linked to an increased risk of cardiovascular complications, the role that rhythmic leukocyte adhesion plays in different vascular beds has not been studied. We evaluated leukocyte recruitment in vivo by using real-time multichannel fluorescence intravital microscopy of a tumor necrosis factor-α-induced acute inflammation model in both murine arterial and venous macrovasculature and microvasculature. These approaches were complemented with genetic, surgical, and pharmacological ablation of sympathetic nerves or adrenergic receptors to assess their relevance for rhythmic leukocyte adhesion. In addition, we genetically targeted the key circadian clock gene In vivo quantitative imaging analyses of acute inflammation revealed a 24-hour rhythm in leukocyte recruitment to arteries and veins of the mouse macrovasculature and microvasculature. Unexpectedly, although in arteries leukocyte adhesion was highest in the morning, it peaked at night in veins. This phase shift was governed by a rhythmic microenvironment and a vessel type-specific oscillatory pattern in the expression of promigratory molecules. Differences in cell adhesion molecules and leukocyte adhesion were ablated when disrupting sympathetic nerves, demonstrating their critical role in this process and the importance of β Together, our findings point to an important and previously unrecognized role of artery-associated sympathetic innervation in governing rhythmicity in vascular inflammation in both arteries and veins and its potential implications in the occurrence of time-of-day-dependent vessel type-specific thrombotic events.
Sections du résumé
BACKGROUND
The incidence of acute cardiovascular complications is highly time-of-day dependent. However, the mechanisms driving rhythmicity of ischemic vascular events are unknown. Although enhanced numbers of leukocytes have been linked to an increased risk of cardiovascular complications, the role that rhythmic leukocyte adhesion plays in different vascular beds has not been studied.
METHODS
We evaluated leukocyte recruitment in vivo by using real-time multichannel fluorescence intravital microscopy of a tumor necrosis factor-α-induced acute inflammation model in both murine arterial and venous macrovasculature and microvasculature. These approaches were complemented with genetic, surgical, and pharmacological ablation of sympathetic nerves or adrenergic receptors to assess their relevance for rhythmic leukocyte adhesion. In addition, we genetically targeted the key circadian clock gene
RESULTS
In vivo quantitative imaging analyses of acute inflammation revealed a 24-hour rhythm in leukocyte recruitment to arteries and veins of the mouse macrovasculature and microvasculature. Unexpectedly, although in arteries leukocyte adhesion was highest in the morning, it peaked at night in veins. This phase shift was governed by a rhythmic microenvironment and a vessel type-specific oscillatory pattern in the expression of promigratory molecules. Differences in cell adhesion molecules and leukocyte adhesion were ablated when disrupting sympathetic nerves, demonstrating their critical role in this process and the importance of β
CONCLUSIONS
Together, our findings point to an important and previously unrecognized role of artery-associated sympathetic innervation in governing rhythmicity in vascular inflammation in both arteries and veins and its potential implications in the occurrence of time-of-day-dependent vessel type-specific thrombotic events.
Identifiants
pubmed: 31401849
doi: 10.1161/CIRCULATIONAHA.119.040232
pmc: PMC6756975
mid: NIHMS1537614
doi:
Substances chimiques
ADRB2 protein, mouse
0
Receptors, Adrenergic, beta-2
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1100-1114Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK056638
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK112976
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL069438
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL116340
Pays : United States
Références
Cell. 2001 Jun 1;105(5):683-94
pubmed: 11389837
Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3047-51
pubmed: 11880644
Acta Biol Hung. 2002;53(1-2):229-44
pubmed: 12064774
Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5339-46
pubmed: 14963227
Annu Rev Immunol. 2004;22:891-928
pubmed: 15032599
Arterioscler Thromb Vasc Biol. 2005 Apr;25(4):658-70
pubmed: 15662026
Microcirculation. 2005 Mar;12(2):151-60
pubmed: 15824037
Clin Exp Hypertens. 2005 Feb-Apr;27(2-3):307-11
pubmed: 15835394
Cell Metab. 2005 Nov;2(5):297-307
pubmed: 16271530
Am J Physiol Regul Integr Comp Physiol. 2006 Apr;290(4):R1128-35
pubmed: 16357102
Am J Physiol Heart Circ Physiol. 2006 Nov;291(5):H2116-25
pubmed: 16766643
Nat Rev Immunol. 2007 Sep;7(9):678-89
pubmed: 17717539
Arterioscler Thromb Vasc Biol. 2008 Jan;28(1):121-6
pubmed: 17975121
Nature. 2008 Mar 27;452(7186):442-7
pubmed: 18256599
Circulation. 2008 Apr 22;117(16):2087-95
pubmed: 18413500
Nat Med. 2009 Apr;15(4):384-91
pubmed: 19305412
PLoS One. 2009 May 21;4(5):e5650
pubmed: 19478857
Annu Rev Physiol. 2010;72:517-49
pubmed: 20148687
Circ Res. 2010 Mar 19;106(5):833-41
pubmed: 20299673
Physiol Rev. 2010 Jul;90(3):1063-102
pubmed: 20664079
Proc Natl Acad Sci U S A. 2012 Jan 10;109(2):582-7
pubmed: 22184247
Immunity. 2012 Aug 24;37(2):290-301
pubmed: 22863835
Nat Immunol. 2013 Jan;14(1):41-51
pubmed: 23179077
Nat Rev Immunol. 2013 Mar;13(3):190-8
pubmed: 23391992
Science. 2013 Sep 27;341(6153):1483-8
pubmed: 23970558
Adv Pharmacol. 2013;68:115-39
pubmed: 24054142
Nature. 2013 Oct 31;502(7473):637-43
pubmed: 24107994
Blood. 2014 Jan 23;123(4):590-3
pubmed: 24200683
Circ Res. 2014 Feb 28;114(5):770-9
pubmed: 24366169
Immunity. 2014 Feb 20;40(2):178-86
pubmed: 24560196
Nat Med. 2014 Aug;20(8):919-26
pubmed: 25064128
Proc Natl Acad Sci U S A. 2015 Jun 9;112(23):7231-6
pubmed: 25995365
Nature. 2015 Sep 24;525(7570):528-32
pubmed: 26374999
Nat Rev Immunol. 2015 Nov;15(11):692-704
pubmed: 26471775
Immunol Rev. 2016 Sep;273(1):61-75
pubmed: 27558328
J Exp Med. 2016 Nov 14;213(12):2567-2574
pubmed: 27799619
N Engl J Med. 1985 Nov 21;313(21):1315-22
pubmed: 2865677
Nat Rev Immunol. 2018 Jul;18(7):423-437
pubmed: 29662121
Acta Physiol Pharmacol Latinoam. 1987;37(3):305-19
pubmed: 3332531
J Exp Med. 1994 Jul 1;180(1):95-109
pubmed: 7911822
Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7562-7
pubmed: 9636189