Knockout of Canopy 2 activates p16
Adaptor Proteins, Signal Transducing
/ genetics
Animals
Cell Proliferation
/ genetics
Cyclin-Dependent Kinase Inhibitor p16
/ genetics
Heart
/ physiology
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
/ genetics
Myocardium
/ metabolism
Phosphorylation
/ genetics
Signal Transduction
/ genetics
Up-Regulation
/ genetics
Canopy 2
Cardiac repair
Heart failure
Myocardial infarction
p16(INK4a)
Journal
Journal of molecular and cellular cardiology
ISSN: 1095-8584
Titre abrégé: J Mol Cell Cardiol
Pays: England
ID NLM: 0262322
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
13
09
2018
revised:
14
02
2019
accepted:
18
04
2019
pubmed:
3
5
2019
medline:
24
6
2020
entrez:
4
5
2019
Statut:
ppublish
Résumé
Cardiac repair depends on angiogenesis and cell proliferation. Previously we identified Canopy 2 (CNPY2) as a secreted angiogenic growth factor which promotes neovascularization. We investigated the role of CNPY2 in cardiac repair following myocardial infarction (MI) and the possible mediators involved using Cnpy2 knockout (KO) mice and human cardiac tissue. Cardiac tissue from patients with end-stage heart failure had significantly lower endogenous CNPY2 expression compared to samples from control patients. CNPY2 expression in mouse hearts significantly decreased following MI. Significantly less leukocyte and endothelial cell proliferation was found in Cnpy2 KO than wild-type (WT) mice post MI which contributed to impaired angiogenesis, tissue repair, and decreased cardiac function (fractional shortening: WT: 21.1 ± 2.1% vs. KO: 16.4 ± 1.6%, p < .01 at day 28 post MI). RT-qPCR revealed significantly increased p16 Cardiac injury and progressive heart failure were associated with decreased CNPY2 levels in both humans and mice. Knockout of Cnpy2 resulted in up-regulation of p16
Sections du résumé
BACKGROUND
Cardiac repair depends on angiogenesis and cell proliferation. Previously we identified Canopy 2 (CNPY2) as a secreted angiogenic growth factor which promotes neovascularization. We investigated the role of CNPY2 in cardiac repair following myocardial infarction (MI) and the possible mediators involved using Cnpy2 knockout (KO) mice and human cardiac tissue.
METHODS AND RESULTS
Cardiac tissue from patients with end-stage heart failure had significantly lower endogenous CNPY2 expression compared to samples from control patients. CNPY2 expression in mouse hearts significantly decreased following MI. Significantly less leukocyte and endothelial cell proliferation was found in Cnpy2 KO than wild-type (WT) mice post MI which contributed to impaired angiogenesis, tissue repair, and decreased cardiac function (fractional shortening: WT: 21.1 ± 2.1% vs. KO: 16.4 ± 1.6%, p < .01 at day 28 post MI). RT-qPCR revealed significantly increased p16
CONCLUSIONS
Cardiac injury and progressive heart failure were associated with decreased CNPY2 levels in both humans and mice. Knockout of Cnpy2 resulted in up-regulation of p16
Identifiants
pubmed: 31047986
pii: S0022-2828(18)30926-X
doi: 10.1016/j.yjmcc.2019.04.018
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
CDKN2A protein, human
0
CNPY2 protein, human
0
Cyclin-Dependent Kinase Inhibitor p16
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
36-48Subventions
Organisme : CIHR
ID : 332652
Pays : Canada
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.