title: Effects of apelin on the cardiovascular system.
abstract: Apelin is an endogenous peptide acting on the APJ receptor. It consists of several isoforms characterized by different numbers of amino acids. The number of amino acids in the active isoforms range from 36 to 12. Apelin-13 and, to a lesser extent, apelin-36 are considered the most active isoforms with the greatest activity on the cardiovascular homeostasis. The effects normally exerted by the basal level of endogenous apelin can be enhanced not only by its up-regulation, but may also by its exogenous administration. The present review considers the effects of apelin on various aspects of the cardiovascular function, such as cardiac development, vasomotor tone, angiogenesis, myocardial inotropy in healthy and failing hearts as well as the prevention of ischemia-reperfusion injury, cardiac fibrosis and remodeling. Also the biphasic changes in apelin level during the evolution of heart failure are considered. Although the positive inotropic effect exerted by apelin in normal and failing hearts would suggest the use of this peptide in the treatment of heart failure, the limited duration and extent of its effect do not support this possibility, unless a long-lasting (6 h) infusion is performed to overcome the limit of its short life. However, although the data on the characteristics of the inotropic activity do not provide a strong support for the treatment of active heart failure, apelin may be used in the prevention of heart failure because of its activity in limiting the consequences of myocardial ischemia such as infarct size and cardiac remodeling.
authors: Department of Neuroscience, University of Turin, C.so Raffaello 30, 10125, Turin, Italy.
authors: Anna
authors: A
authors: Folino
authors: Pier Giorgio
authors: PG
authors: Montarolo
authors: Michele
authors: M
authors: Samaja
authors: Raffaella
authors: R
authors: Rastaldo
mesh_terms: D000818:Animals; D000073861:Apelin; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*
chemical_list: C115436:APLN protein, human; D000073861:Apelin; D036341:Intercellular Signaling Peptides and Proteins
references: Mech Dev. 1996 Oct;59(2):129-40
references: 8951791
references: Eur J Pharmacol. 2006 Dec 28;553(1-3):222-8
references: 17055480
references: Gene. 1993 Dec 22;136(1-2):355-60
references: 8294032
references: PLoS One. 2013 Dec 26;8(12):e83051
references: 24386141
references: Can J Physiol Pharmacol. 2013 Sep;91(9):708-14
references: 23984675
references: Cell Signal. 2005 Apr;17(4):415-26
references: 15601620
references: Br J Pharmacol. 2013 Mar;168(5):1104-17
references: 22935142
references: Circulation. 2010 Aug 17;122(7):717-28, 18 p following 728
references: 20679547
references: Am J Physiol Heart Circ Physiol. 2011 Oct;301(4):H1471-86
references: 21803944
references: Biochem Biophys Res Commun. 1998 Oct 20;251(2):471-6
references: 9792798
references: PLoS One. 2014 Apr 02;9(4):e93473
references: 24695532
references: Hypertens Res. 2011 Jun;34(6):701-6
references: 21412239
references: J Clin Invest. 2011 Sep;121(9):3735-46
references: 21821917
references: J Cardiovasc Pharmacol. 1984;6 Suppl 4:S575-86
references: 6083400
references: Cardiol Res Pract. 2012;2012:823193
references: 22655211
references: PLoS One. 2012;7(6):e38328
references: 22675543
references: Eur J Pharmacol. 2003 Jun 6;470(3):171-5
references: 12798955
references: Regul Pept. 2005 Feb 15;125(1-3):55-9
references: 15582714
references: Nat Med. 2002 Nov;8(11):1303-9
references: 12379849
references: J Renin Angiotensin Aldosterone Syst. 2006 Dec;7(4):212-6
references: 17318790
references: Circ Res. 2002 Sep 6;91(5):434-40
references: 12215493
references: Mol Cell Biol. 2004 Sep;24(18):8007-17
references: 15340063
references: Basic Res Cardiol. 2007 Nov;102(6):518-28
references: 17694254
references: Mech Dev. 1999 Jun;84(1-2):199-203
references: 10473142
references: J Hypertens. 2013 Apr;31(4):730-8
references: 23425706
references: Gene Expr Patterns. 2003 Aug;3(4):467-72
references: 12915314
references: Dev Biol. 2006 Oct 1;298(1):188-200
references: 16876154
references: J Am Heart Assoc. 2013 Jul 01;2(4):e000249
references: 23817469
references: Mech Dev. 2002 Jan;110(1-2):183-6
references: 11744380
references: Biochem Biophys Res Commun. 2003 Aug 29;308(3):480-5
references: 12914775
references: Arq Bras Cardiol. 2008 May;90(5):343-9
references: 18516406
references: Acta Biochim Biophys Sin (Shanghai). 2014 Feb;46(2):100-11
references: 24374773
references: Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10464-9
references: 15231996
references: Blood. 2010 Apr 15;115(15):3166-74
references: 20185589
references: Nature. 2002 Jan 10;415(6868):198-205
references: 11805843
references: J Clin Invest. 1987 Dec;80(6):1728-34
references: 3680525
references: Circulation. 2002 May 7;105(18):2185-91
references: 11994253
references: Dev Biol. 2006 Aug 1;296(1):177-89
references: 16750822
references: J Card Fail. 2013 Jul;19(7):509-16
references: 23834927
references: Peptides. 2007 Mar;28(3):708-18
references: 17109997
references: Circ Heart Fail. 2013 May;6(3):482-91
references: 23519586
references: J Biol Chem. 2004 Jun 18;279(25):26274-9
references: 15087458
references: Cardiovasc Res. 2005 Jan 1;65(1):73-82
references: 15621035
references: Antioxid Redox Signal. 2011 Mar 1;14(5):909-22
references: 20615122
references: J Renin Angiotensin Aldosterone Syst. 2004 Sep;5 Suppl 1:S2-6
references: 15526238
references: J Am Soc Nephrol. 2008 May;19(5):1015-24
references: 18272843
references: J Clin Invest. 2013 Dec;123(12 ):5203-11
references: 24177423
references: Nature. 2012 Aug 16;488(7411):394-8
references: 22810587
references: Lab Invest. 2011 Apr;91(4):565-78
references: 21116240
references: J Mol Neurosci. 2012 Sep;48(1):201-8
references: 22638858
references: Neurochem Int. 2013 Nov;63(6):535-40
references: 24083989
references: J Biol Chem. 2002 Apr 26;277(17):14838-43
references: 11815627
references: Chin Med J (Engl). 2009 Oct 5;122(19):2360-5
references: 20079140
references: Am J Physiol Heart Circ Physiol. 2008 Jun;294(6):H2540-6
references: 18424641
references: Cardiovasc Drugs Ther. 2007 Dec;21(6):409-14
references: 17924178
references: J Am Coll Cardiol. 2008 Sep 9;52(11):908-13
references: 18772060
references: J Cardiovasc Pharmacol. 2010 Jan;55(1):83-8
references: 19904215
references: Hypertension. 2012 Feb;59(2):300-7
references: 22184331
references: Cardiovasc Res. 2004 Feb 15;61(3):365-71
references: 14962469
references: Clin Sci (Lond). 2007 Apr;112(8):417-28
references: 17346243
references: Circ Res. 2000 Jun 23;86(12):1259-65
references: 10864917
references: Br J Pharmacol. 2001 Mar;132(6):1255-60
references: 11250876
references: Circ J. 2012;76(1):137-44
references: 22082814
references: Anal Biochem. 2013 Nov 1;442(1):1-9
references: 23872001
references: J Renin Angiotensin Aldosterone Syst. 2006 Mar;7(1):3-14
references: 17083068
references: Amino Acids. 2010 Nov;39(5):1193-200
references: 20495838
references: Stem Cell Res. 2012 May;8(3):357-67
references: 22289418
references: Apoptosis. 2007 Jan;12(1):247-54
references: 17136493
references: Pharmacol Rev. 2000 Mar;52(1):11-34
references: 10699153
references: Biochem Biophys Res Commun. 2007 Jun 15;357(4):889-95
references: 17466269
references: Regul Pept. 2008 Feb 7;146(1-3):271-7
references: 18022257
references: Eur J Heart Fail. 2006 Jun;8(4):355-60
references: 16464638
references: Clin Sci (Lond). 2014 Jun;126(12 ):815-27
references: 24593683
references: Neurosci Lett. 2014 May 7;568:44-9
references: 24686182
references: Regul Pept. 2004 May 15;118(3):119-25
references: 15003827
references: FASEB J. 2007 Jun;21(8):1821-30
references: 17341685
references: Regul Pept. 2001 Jun 15;99(2-3):87-92
references: 11384769
references: Circulation. 2004 Sep 14;110(11 Suppl 1):II187-93
references: 15364861
references: Cardiovasc Res. 2007 Jun 1;74(3):388-95
references: 17359956
references: Life Sci. 2007 Aug 16;81(10):779-93
references: 17707439
references: Science. 1997 May 30;276(5317):1404-7
references: 9162005
references: Biochem Pharmacol. 2008 May 15;75(10):1882-92
references: 18272138
references: Circ Res. 1996 Jan;78(1):91-101
references: 8603511
references: Regul Pept. 2006 Jan 15;133(1-3):147-54
references: 16278022
references: J Neurochem. 2000 Jan;74(1):34-41
references: 10617103
references: Circ Res. 2013 Jun 21;113(1):22-31
references: 23603510
references: EMBO J. 2008 Feb 6;27(3):522-34
references: 18200044
references: Peptides. 2010 Sep;31(9):1772-8
references: 20561551
references: Pulm Circ. 2011 Jul-Sep;1(3):334-46
references: 22140623
references: Mol Med Rep. 2014 May;9(5):1590-6
references: 24573187
references: Arterioscler Thromb Vasc Biol. 2008 Oct;28(10):1687-8
references: 18799795
references: Physiol Rev. 2010 Jul;90(3):1013-62
references: 20664078
references: J Hypertens. 2014 Apr;32(4):771-83
references: 24463937
references: Arterioscler Thromb Vasc Biol. 2006 Jun;26(6):1267-72
references: 16556853
references: Am J Physiol Heart Circ Physiol. 2011 Jun;300(6):H2308-15
references: 21378145
references: Biochem Biophys Res Commun. 2004 Dec 10;325(2):395-400
references: 15530405
references: Circ Res. 1999 Oct 29;85(9):777-86
references: 10532945
references: Circ Res. 2000 Sep 1;87(5):E1-9
references: 10969042
references: Eur Heart J. 2012 Sep;33(18):2360-9
references: 22028387
references: Acta Biochim Biophys Sin (Shanghai). 2014 Jul;46(7):620-2
references: 24829400
references: Br J Pharmacol. 2010 Aug;160(7):1785-95
references: 20649580
references: Pharmacol Ther. 2007 Nov;116(2):173-91
references: 17681609
references: Circ Res. 2011 Apr 29;108(9):1122-32
references: 21527742
references: Mol Med Rep. 2013 May;7(5):1371-5
references: 23525196
references: Peptides. 2009 Jun;30(6):1144-52
references: 19463748
references: Mol Cell Biochem. 2014 Jun;391(1-2):241-50
references: 24599747
references: Hypertension. 2009 Sep;54(3):598-604
references: 19597036
references: Circ Res. 2014 Jan 17;114(2):283-94
references: 24226423
references: Circulation. 2000 Nov 14;102(20 Suppl 4):IV69-74
references: 11080134
references: Oncogene. 2007 Dec 6;26(55):7692-9
references: 17563744
references: Virology. 2003 Dec 5;317(1):84-94
references: 14675627
references: Circulation. 2002 May 7;105(18):2133-5
references: 11994243
references: J Biol Chem. 2000 Jul 14;275(28):21061-7
references: 10777510
references: Dev Cell. 2013 Dec 23;27(6):672-80
references: 24316148
references: Pharmacol Ther. 2005 Aug;107(2):198-211
references: 15907343
references: J Clin Invest. 2008 Oct;118(10):3343-54
references: 18769630
references: Am J Physiol Heart Circ Physiol. 2009 Nov;297(5):H1904-13
references: 19767528
references: J Physiol Pharmacol. 2013 Aug;64(4):423-8
references: 24101388