PMID- 31093829
OWN - NLM
STAT- MEDLINE
DCOM- 20200521
LR  - 20200521
IS  - 2509-2723 (Electronic)
IS  - 2509-2715 (Print)
IS  - 2509-2723 (Linking)
VI  - 41
IP  - 5
DP  - 2019 Oct
TI  - Systolic hypertension-induced neurovascular unit disruption magnifies vascular 
      cognitive impairment in middle-age atherosclerotic LDLr(-/-):hApoB(+/+) mice.
PG  - 511-532
LID - 10.1007/s11357-019-00070-6 [doi]
AB  - Cognitive functions are dependent upon intercommunications between the cellular 
      components of the neurovascular unit (NVU). Vascular risk factors are associated 
      with a more rapid rate of cognitive decline with aging and cerebrovascular 
      diseases magnify both the incidence and the rate of cognitive decline. The causal 
      relationship between vascular risk factors and injury to the NVU is, however, 
      lacking. We hypothesized that vascular risk factors, such as hypertension and 
      dyslipidemia, promote disruption of the NVU leading to early cognitive 
      impairment. We compared brain structure and cerebrovascular functions of 1-year 
      old (middle-aged) male wild-type (WT) and atherosclerotic hypertensive 
      (LDLr(-/-):hApoB(+/+), ATX) mice. In addition, mice were subjected, or not, to a 
      transverse aortic constriction (TAC) for 6 weeks to assess the acute impact of an 
      increase in systolic blood pressure on the NVU and cognitive functions. Compared 
      with WT mice, ATX mice prematurely developed cognitive decline associated with 
      cerebral micro-hemorrhages, loss of microvessel density and brain atrophy, 
      cerebral endothelial cell senescence and dysfunction, brain inflammation, and 
      oxidative stress associated with blood-brain barrier leakage and brain 
      hypoperfusion. These data suggest functional disturbances in both vascular and 
      parenchymal components of the NVU. Exposure to TAC-induced systolic hypertension 
      promoted cerebrovascular damage and cognitive decline in WT mice, similar to 
      those observed in sham-operated ATX mice; TAC exacerbated the existing 
      cerebrovascular dysfunctions and cognitive failure in ATX mice. Thus, a 
      hemodynamic stress such as systolic hypertension could initiate the cascade 
      involving cerebrovascular injury and NVU deregulation and lead to cognitive 
      decline, a process accelerated in atherosclerotic mice.
FAU - de Montgolfier, Olivia
AU  - de Montgolfier O
AD  - Faculty of Medicine, Department of pharmacology and physiology, Universite de 
      Montreal, Montreal, QC, Canada.
AD  - Research Center, Montreal Heart Institute, 5000 rue Belanger Est, Montreal, QC, 
      H1T 1C8, Canada.
FAU - Pouliot, Philippe
AU  - Pouliot P
AD  - Research Center, Montreal Heart Institute, 5000 rue Belanger Est, Montreal, QC, 
      H1T 1C8, Canada.
AD  - Ecole Polytechnique de Montreal, Montreal, QC, Canada.
FAU - Gillis, Marc-Antoine
AU  - Gillis MA
AD  - Research Center, Montreal Heart Institute, 5000 rue Belanger Est, Montreal, QC, 
      H1T 1C8, Canada.
FAU - Ferland, Guylaine
AU  - Ferland G
AD  - Research Center, Montreal Heart Institute, 5000 rue Belanger Est, Montreal, QC, 
      H1T 1C8, Canada.
AD  - Faculty of Medicine, Department of nutrition, Universite de Montreal, Montreal, 
      QC, Canada.
FAU - Lesage, Frederic
AU  - Lesage F
AD  - Research Center, Montreal Heart Institute, 5000 rue Belanger Est, Montreal, QC, 
      H1T 1C8, Canada.
AD  - Ecole Polytechnique de Montreal, Montreal, QC, Canada.
FAU - Thorin-Trescases, Nathalie
AU  - Thorin-Trescases N
AD  - Research Center, Montreal Heart Institute, 5000 rue Belanger Est, Montreal, QC, 
      H1T 1C8, Canada.
FAU - Thorin, Eric
AU  - Thorin E
AUID- ORCID: 0000-0001-5827-8935
AD  - Faculty of Medicine, Department of pharmacology and physiology, Universite de 
      Montreal, Montreal, QC, Canada. eric.thorin@umontreal.ca.
AD  - Research Center, Montreal Heart Institute, 5000 rue Belanger Est, Montreal, QC, 
      H1T 1C8, Canada. eric.thorin@umontreal.ca.
AD  - Faculty of Medicine, Department of surgery, Universite de Montreal, Montreal, QC, 
      Canada. eric.thorin@umontreal.ca.
LA  - eng
GR  - MOP 133649/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190515
PL  - Switzerland
TA  - Geroscience
JT  - GeroScience
JID - 101686284
SB  - IM
MH  - Animals
MH  - Atherosclerosis/*physiopathology
MH  - Atrophy
MH  - Blood-Brain Barrier/physiopathology
MH  - Brain/*blood supply/pathology
MH  - Cellular Senescence/physiology
MH  - Cerebral Hemorrhage/physiopathology
MH  - Cognitive Dysfunction/*physiopathology
MH  - Dementia, Vascular/*physiopathology
MH  - Disease Models, Animal
MH  - Endothelial Cells/pathology
MH  - Hypertension/*physiopathology
MH  - Mice, Transgenic
MH  - Microvessels/pathology
MH  - Oxidative Stress/physiology
MH  - Systole/*physiology
PMC - PMC6885084
OTO - NOTNLM
OT  - 7T-MRI
OT  - Apoptosis
OT  - Blood-brain barrier
OT  - Carotid stiffness
OT  - Endothelial function
OT  - Hypertension
OT  - Senescence
OT  - Transverse aortic constriction
OT  - VCID
COIS- The authors declare that they have no conflict of interest.
EDAT- 2019/05/17 06:00
MHDA- 2020/05/22 06:00
PMCR- 2019/05/15
CRDT- 2019/05/17 06:00
PHST- 2019/03/25 00:00 [received]
PHST- 2019/04/16 00:00 [accepted]
PHST- 2019/05/17 06:00 [pubmed]
PHST- 2020/05/22 06:00 [medline]
PHST- 2019/05/17 06:00 [entrez]
PHST- 2019/05/15 00:00 [pmc-release]
AID - 10.1007/s11357-019-00070-6 [pii]
AID - 70 [pii]
AID - 10.1007/s11357-019-00070-6 [doi]
PST - ppublish
SO  - Geroscience. 2019 Oct;41(5):511-532. doi: 10.1007/s11357-019-00070-6. Epub 2019 
      May 15.