PMID- 34046769
OWN - NLM
STAT- MEDLINE
DCOM- 20220211
LR  - 20220531
IS  - 1573-7209 (Electronic)
IS  - 0969-6970 (Print)
IS  - 0969-6970 (Linking)
VI  - 24
IP  - 4
DP  - 2021 Nov
TI  - Pericyte hypoxia-inducible factor-1 (HIF-1) drives blood-brain barrier disruption 
      and impacts acute ischemic stroke outcome.
PG  - 823-842
LID - 10.1007/s10456-021-09796-4 [doi]
AB  - Pericytes play essential roles in blood-brain barrier integrity and their 
      dysfunction is implicated in neurological disorders such as stroke although the 
      underlying mechanisms remain unknown. Hypoxia-inducible factor-1 (HIF-1), a 
      master regulator of injury responses, has divergent roles in different cells 
      especially during stress scenarios. On one hand HIF-1 is neuroprotective but on 
      the other it induces vascular permeability. Since pericytes are critical for 
      barrier stability, we asked if pericyte HIF-1 signaling impacts barrier integrity 
      and injury severity in a mouse model of ischemic stroke. We show that pericyte 
      HIF-1 loss of function (LoF) diminishes ischemic damage and barrier permeability 
      at 3 days reperfusion. HIF-1 deficiency preserved barrier integrity by reducing 
      pericyte death thereby maintaining vessel coverage and junctional protein 
      organization, and suppressing vascular remodeling. Importantly, considerable 
      improvements in sensorimotor function were observed in HIF-1 LoF mice indicating 
      that better vascular functionality post stroke improves outcome. Thus, boosting 
      vascular integrity by inhibiting pericytic HIF-1 activation and/or increasing 
      pericyte survival may be a lucrative option to accelerate recovery after severe 
      brain injury.
CI  - (c) 2021. The Author(s).
FAU - Tsao, Chih-Chieh
AU  - Tsao CC
AD  - Institute of Veterinary Physiology and Zurich Center for Integrative Human 
      Physiology (ZIHP), University of Zurich, Winterthurerstrasse 260, 8057, Zurich, 
      Switzerland.
FAU - Baumann, Julia
AU  - Baumann J
AD  - Institute of Veterinary Physiology and Zurich Center for Integrative Human 
      Physiology (ZIHP), University of Zurich, Winterthurerstrasse 260, 8057, Zurich, 
      Switzerland.
FAU - Huang, Sheng-Fu
AU  - Huang SF
AD  - Institute of Veterinary Physiology and Zurich Center for Integrative Human 
      Physiology (ZIHP), University of Zurich, Winterthurerstrasse 260, 8057, Zurich, 
      Switzerland.
FAU - Kindler, Diana
AU  - Kindler D
AD  - Institute for Biomedical Engineering, ETH Zurich, Wolfgang-Pauli-Strasse 27, 
      8093, Zurich, Switzerland.
FAU - Schroeter, Aileen
AU  - Schroeter A
AD  - Institute for Biomedical Engineering, ETH Zurich, Wolfgang-Pauli-Strasse 27, 
      8093, Zurich, Switzerland.
FAU - Kachappilly, Nicole
AU  - Kachappilly N
AD  - Institute of Veterinary Physiology and Zurich Center for Integrative Human 
      Physiology (ZIHP), University of Zurich, Winterthurerstrasse 260, 8057, Zurich, 
      Switzerland.
FAU - Gassmann, Max
AU  - Gassmann M
AD  - Institute of Veterinary Physiology and Zurich Center for Integrative Human 
      Physiology (ZIHP), University of Zurich, Winterthurerstrasse 260, 8057, Zurich, 
      Switzerland.
FAU - Rudin, Markus
AU  - Rudin M
AD  - Institute for Biomedical Engineering, ETH Zurich, Wolfgang-Pauli-Strasse 27, 
      8093, Zurich, Switzerland.
FAU - Ogunshola, Omolara O
AU  - Ogunshola OO
AD  - Institute of Veterinary Physiology and Zurich Center for Integrative Human 
      Physiology (ZIHP), University of Zurich, Winterthurerstrasse 260, 8057, Zurich, 
      Switzerland. larao@access.uzh.ch.
LA  - eng
GR  - 31003A_150062/Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen 
      Forschung/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210527
PL  - Germany
TA  - Angiogenesis
JT  - Angiogenesis
JID - 9814575
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier
MH  - *Brain Ischemia
MH  - Hypoxia
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics
MH  - *Ischemic Stroke
MH  - Mice
MH  - Pericytes
MH  - *Stroke
PMC - PMC8487886
OTO - NOTNLM
OT  - Cerebral ischemia
OT  - Pericyte coverage
OT  - Pericyte death
OT  - Vascular permeability
COIS- The authors declare that they have no conflict of interest.
EDAT- 2021/05/29 06:00
MHDA- 2022/02/12 06:00
PMCR- 2021/05/27
CRDT- 2021/05/28 07:36
PHST- 2020/12/15 00:00 [received]
PHST- 2021/05/04 00:00 [accepted]
PHST- 2021/05/29 06:00 [pubmed]
PHST- 2022/02/12 06:00 [medline]
PHST- 2021/05/28 07:36 [entrez]
PHST- 2021/05/27 00:00 [pmc-release]
AID - 10.1007/s10456-021-09796-4 [pii]
AID - 9796 [pii]
AID - 10.1007/s10456-021-09796-4 [doi]
PST - ppublish
SO  - Angiogenesis. 2021 Nov;24(4):823-842. doi: 10.1007/s10456-021-09796-4. Epub 2021 
      May 27.