The urotensin II receptor antagonist DS37001789 ameliorates mortality in pressure-overload mice with heart failure.
Biochemistry
Biological sciences
Cardiology
Cardiovascular system
Diabetes
Endocrinology
GPR14
Health sciences
Heart failure
Medicine
Pharmaceutical science
Physiology
Renal system
Transverse aortic constriction
Urotensin II
Journal
Heliyon
ISSN: 2405-8440
Titre abrégé: Heliyon
Pays: England
ID NLM: 101672560
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
received:
27
12
2019
revised:
14
01
2020
accepted:
30
01
2020
entrez:
15
2
2020
pubmed:
15
2
2020
medline:
15
2
2020
Statut:
epublish
Résumé
This study was designed to evaluate the effects of DS37001789, a novel and highly potent urotensin II (U-II) receptor (GPR14) antagonist, against mortality, hypertrophy, and cardiac dysfunction in pressure-overload hypertrophy by transverse aortic constriction (TAC) in mice. In addition, we analyzed the phenotype of GPR14 knockout (KO) mice after TAC induction to confirm the contribution of the U-II/GPR14 system. The oral administration of 0.2% DS37001789 to TAC mice for 12 weeks significantly ameliorated the mortality rate and 0.2% DS37001789 for 4 weeks significantly improved cardiac function by pressure-volume analysis. GPR14 expression was significantly upregulated in the left ventricle in the TAC mice treated with 0.2% DS37001789. Moreover, we confirmed that the significant amelioration of mortality was accomplished by the inhibition of cardiac enlargement and the improvement of cardiac function in GPR14 KO mice after TAC surgery. These results suggest that the U-II/GPR14 system contributes to the progression of heart failure and its blockade ameliorates the mortality via improved cardiac function. The U-II/GPR14 system may thus be an attractive target for treating heart failure with pathological cardiac hypertrophy and DS37001789 may be a novel therapeutic agent for heart failure in patients with pressure-overload conditions such as hypertension and aortic valve stenosis.
Identifiants
pubmed: 32055741
doi: 10.1016/j.heliyon.2020.e03352
pii: S2405-8440(20)30197-3
pii: e03352
pmc: PMC7005433
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e03352Informations de copyright
© 2020 The Authors.
Références
Am J Physiol Heart Circ Physiol. 2003 Oct;285(4):H1576-81
pubmed: 12791592
BMC Cancer. 2010 Mar 22;10:105
pubmed: 20307299
J Mol Cell Cardiol. 2006 Aug;41(2):285-95
pubmed: 16797584
Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15803-8
pubmed: 9861051
Peptides. 2010 Aug;31(8):1523-30
pubmed: 20452383
Peptides. 2003 Feb;24(2):301-6
pubmed: 12668216
Br J Pharmacol. 2008 Oct;155(3):374-86
pubmed: 18587423
J Cardiovasc Pharmacol. 2019 Jan;73(1):15-21
pubmed: 30608334
Nature. 1999 Sep 16;401(6750):282-6
pubmed: 10499587
Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8277-81
pubmed: 1832775
Int J Cardiol. 2004 Mar;94(1):93-7
pubmed: 14996481
Front Pharmacol. 2011 Jul 22;2:38
pubmed: 21811463
Circulation. 2002 Dec 3;106(23):2877-80
pubmed: 12460864
J Exp Clin Cancer Res. 2014 Jun 03;33:48
pubmed: 24893613
Br J Pharmacol. 2015 May;172(10):2618-33
pubmed: 25597918
Circulation. 1995 May 1;91(9):2314-8
pubmed: 7729016
Circ Res. 1995 May;76(5):907-14
pubmed: 7729009
Nat Med. 2005 Feb;11(2):214-22
pubmed: 15665834
Circulation. 1994 Jun;89(6):2852-9
pubmed: 8205701
Curr Cancer Drug Targets. 2017;17(2):109-121
pubmed: 27338741
Lancet. 2002 Aug 17;360(9332):545-6
pubmed: 12241661
Cardiovasc Hematol Agents Med Chem. 2008 Apr;6(2):80-91
pubmed: 18473773
Circ Res. 1985 Jul;57(1):84-95
pubmed: 3891127
Peptides. 2006 Jun;27(6):1527-31
pubmed: 16364499
Trends Cardiovasc Med. 2000 Aug;10(6):229-37
pubmed: 11282300
Nat Rev Cardiol. 2011 Dec 06;9(3):147-57
pubmed: 22143079
Peptides. 2001 Jul;22(7):1175-9
pubmed: 11445248
Am J Cardiol. 2011 Apr 1;107(7):1065-70
pubmed: 21296328
J Hypertens. 2004 Jul;22(7):1341-4
pubmed: 15201550
J Am Coll Cardiol. 2016 Sep 20;68(12):1277-80
pubmed: 27634118
Br J Pharmacol. 2000 Aug;130(8):1865-70
pubmed: 10952676
Lancet. 2002 Jun 8;359(9322):1990-7
pubmed: 12076554
Circulation. 1993 Jun;87(6 Suppl):VI17-23
pubmed: 8500235
J Pharmacol Exp Ther. 2008 Aug;326(2):380-7
pubmed: 18456872