PMID- 30745457
OWN - NLM
STAT- MEDLINE
DCOM- 20200128
LR  - 20231213
IS  - 1573-4935 (Electronic)
IS  - 0144-8463 (Print)
IS  - 0144-8463 (Linking)
VI  - 39
IP  - 2
DP  - 2019 Feb 28
TI  - Ablation of both Cx40 and Panx1 results in similar cardiovascular phenotypes 
      exhibited in Cx40 knockout mice.
LID - BSR20182350 [pii]
LID - 10.1042/BSR20182350 [doi]
AB  - Connexins (Cxs) and pannexins (Panxs) are highly regulated large-pore 
      channel-forming proteins that participate in cellular communication via small 
      molecular exchange with the extracellular microenvironment, or in the case of 
      connexins, directly between cells. Given the putative functional overlap between 
      single membrane-spanning connexin hemichannels and Panx channels, and 
      cardiovascular system prevalence, we generated the first Cx40(-/-)Panx1(-/-) 
      mouse with the anticipation that this genetic modification would lead to a severe 
      cardiovascular phenotype. Mice null for both Cx40 and Panx1 produced litter sizes 
      and adult growth progression similar to wild-type (WT), Cx40(-/-) and Panx1(-/-) 
      mice. Akin to Cx40(-/-) mice, Cx40(-/-)Panx1(-/-) mice exhibited cardiac 
      hypertrophy and elevated systolic, diastolic, and mean arterial blood pressure 
      compared with WT and Panx1(-/-) mice; however assessment of left ventricular 
      ejection fraction and fractional shortening revealed no evidence of cardiac 
      dysfunction between groups. Furthermore, Cx40(-/-), Panx1(-/-), and 
      Cx40(-/-)Panx1(-/-) mice demonstrated impaired endothelial-mediated vasodilation 
      of aortic segments to increasing concentrations of methacholine (MCh) compared 
      with WT, highlighting roles for both Cx40 and Panx1 in vascular endothelial cell 
      (EC) function. Surprisingly, elevated kidney renin mRNA expression, plasma renin 
      activity, and extraglomerular renin-producing cell populations found in Cx40(-/-) 
      mice was further exaggerated in double knockout mice. Thus, while gestation and 
      gross development were conserved in Cx40(-/-)Panx1(-/-) mice, they exhibit 
      cardiac hypertrophy, hypertension, and impaired endothelial-mediated vasodilation 
      that phenocopies Cx40(-/-) mice. Nevertheless, the augmented renin homeostasis 
      observed in the double knockout mice suggests that both Cx40 and Panx1 may play 
      an integrative role.
CI  - (c) 2019 The Author(s).
FAU - Novielli-Kuntz, Nicole M
AU  - Novielli-Kuntz NM
AD  - Department of Anatomy and Cell Biology, University of Western Ontario, London, 
      Canada.
FAU - Jelen, Meghan
AU  - Jelen M
AD  - Department of Anatomy and Cell Biology, University of Western Ontario, London, 
      Canada.
FAU - Barr, Kevin
AU  - Barr K
AD  - Department of Anatomy and Cell Biology, University of Western Ontario, London, 
      Canada.
FAU - DeLalio, Leon J
AU  - DeLalio LJ
AD  - Robert M. Berne Cardiovascular Research Center, University of Virginia School of 
      Medicine, Charlottesville, VA, U.S.A.
FAU - Feng, Qingping
AU  - Feng Q
AD  - Department of Physiology and Pharmacology London, ON, Canada.
FAU - Isakson, Brant E
AU  - Isakson BE
AD  - Robert M. Berne Cardiovascular Research Center, University of Virginia School of 
      Medicine, Charlottesville, VA, U.S.A.
FAU - Gros, Robert
AU  - Gros R
AD  - Department of Physiology and Pharmacology London, ON, Canada.
AD  - Robarts Research Institute, Schulich School of Medicine & Dentistry, University 
      of Western Ontario, London, ON, Canada.
FAU - Laird, Dale W
AU  - Laird DW
AUID- ORCID: 0000-0002-4568-3285
AD  - Department of Anatomy and Cell Biology, University of Western Ontario, London, 
      Canada Dale.laird@schulich.uwo.ca.
AD  - Department of Physiology and Pharmacology London, ON, Canada.
LA  - eng
GR  - P01 HL120840/HL/NHLBI NIH HHS/United States
GR  - 130530/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190227
PL  - England
TA  - Biosci Rep
JT  - Bioscience reports
JID - 8102797
RN  - 0 (Connexins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Panx1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Cardiomegaly/*genetics/pathology/physiopathology
MH  - Connexins/*genetics
MH  - Fibrosis
MH  - *Gene Deletion
MH  - Hypertension/*genetics/pathology/physiopathology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myocardium/metabolism/pathology
MH  - Nerve Tissue Proteins/*genetics
MH  - Gap Junction alpha-5 Protein
PMC - PMC6393227
OTO - NOTNLM
OT  - Pannexin 1
OT  - connexin
OT  - gap junctions
COIS- The authors declare that there are no competing interests associated with the 
      manuscript.
EDAT- 2019/02/13 06:00
MHDA- 2020/01/29 06:00
PMCR- 2019/02/27
CRDT- 2019/02/13 06:00
PHST- 2018/11/06 00:00 [received]
PHST- 2019/01/10 00:00 [revised]
PHST- 2019/02/05 00:00 [accepted]
PHST- 2019/02/13 06:00 [pubmed]
PHST- 2020/01/29 06:00 [medline]
PHST- 2019/02/13 06:00 [entrez]
PHST- 2019/02/27 00:00 [pmc-release]
AID - BSR20182350 [pii]
AID - 10.1042/BSR20182350 [doi]
PST - epublish
SO  - Biosci Rep. 2019 Feb 27;39(2):BSR20182350. doi: 10.1042/BSR20182350. Print 2019 
      Feb 28.