Abstract
The molecular mechanisms of midkine (MK) in myocardial damage and the possibility of clinical application of MK for heart failure were assessed. In the acute phase of cardiac ischemia/reperfusion (I/R) injury of mice, MK showed an anti-apoptotic reaction for cardiomyocytes through Bcl-2 and ERK activation. In addition, the damage from pig acute I/R injury was suppressed by catheter injection of MK into the coronary artery. The pig model is the faithful one of clinical case, and thus MK has been suggested to be an important candidate material for the treatment of acute myocardial infarction. MK also prevented ventricular remodeling and improved long-term survival after myocardial infarction in mouse and rat chronic models. The mechanisms of these effects involved MK-induced angiogenesis via the PI3/Akt pathway. Moreover, MK inhibited the cardiac remodeling of non-ischemic myocardial damage induced by rapid pacing in rabbits. MK is thus a potentially important new molecular target for treatment and prevention of heart failure.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Bialik S, Geenen DL, Sasson IE et al (1997) Myocyte apoptosis during acute myocardial infarction in the mouse localizes to hypoxic regions but occurs independently of p53. J Clin Invest 100:1363–1372
Moens AL, Claeys MJ, Timmermans JP et al (2005) Myocardial ischemia/reperfusion-injury, a clinical view on a complex pathophysiological process. Int J Cardiol 100:179–190
Narula J, Haider N, Vimani R et al (1996) Apoptosis in myocytes in end-stage heart failure. N Eng J Med 335:1182–1189
Horiba M, Kadomatsu K, Yasui K et al (2006) Midkine plays a protective role against cardiac ischemia/reperfusion injury through a reduction of apoptotic reaction. Circulation 114:1713–1720
Takenaka H, Horiba M, Ishiguro H et al (2009) Midkine prevents ventricular remodeling and improves long-term survival after myocardial infarction. Am J Physiol Heart Circ Physiol 296:H462–H469
Sumida A, Horiba M, Ishiguro H et al (2010) Midkine gene transfer after myocardial infarction in rats prevents remodelling and ameliorates cardiac dysfunction. Cardiovasc Res 86:113–121
Nakamura T, Mizuno S, Matsumoto K et al (2000) Exogenous HGF. J Clin Invest 106:1511–1519
Parsa CJ, Matsumoto A, Kim J et al (2003) A novel protective effect of erythropoietin in the infarcted heart. J Clin Invest 112:999–1007
Kato K, Yin H, Agata J et al (2003) Adrenomedullin gene delivery attenuates myocardial infarction and apoptosis after ischemia and reperfusion. Am J Physiol Heart Circ Physiol 285:H1506–H1514
Bock-Marquette I, Saxena A, White MD et al (2004) Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature 432:466–472
Qi M, Ikematsu S, Ichihara-Tanaka K et al (2000) Midkine rescues Wilms’ tumor cells from cisplatin-induced apoptosis: regulation of Bcl-2 expression by Midkine. J Biochem-Tokyo 127:269–277
Owada K, Sanjo N, Kobayashi T et al (1999) Midkine inhibits caspase-dependent apoptosis via the activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase in cultured neurons. J Neurochem 73:2084–2092
Ishiguro H, Horiba M, Takenaka H et al (2011) A single intracoronary injection of midkine reduces ischemia/reperfusion injury in swine hearts: a novel therapeutic approach for acute coronary syndrome. Front Physiol 2:27
Krzeminski TF, Nozynski JK, Grzyb J et al (2005) Angiogenesis and cardioprotection after TNFalpha-inducer-Tolpa Peat Preparation treatment in rat’s hearts after experimental myocardial infarction in vivo. Vascul Pharmacol 43:164–170
Wang Y, Ahmad N, Wani MA et al (2004) Hepatocyte growth factor prevents ventricular remodeling and dysfunction in mice via Akt pathway and angiogenesis. J Mol Cell Cardiol 37:1041–1052
Muramatsu T (2002) Midkine and pleiotrophin: two related proteins involved in development, survival, inflammation and tumorigenesis. J Biochem-Tokyo 132:359–371
Shiojima I, Walsh K (2002) Role of Akt signaling in vascular homeostasis and angiogenesis. Circ Res 90:1243–1250
Carmeliet P, Dor Y, Herbert JM et al (1998) Role of HIF-1 alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 395:525
Gerber HP, Condorelli F, Park J et al (1997) Differential transcriptional regulation of the two vascular endothelial growth factor receptor genes. Flt-1, but not Flk-1/KDR, is up-regulated by hypoxia. J Biol Chem 272:23659–23667
Li J, Post M, Volk R et al (2000) PR39, a peptide regulator of angiogenesis. Nat Med 6:49–55
Martin C, Yu AY, Jiang BH et al (1998) Cardiac hypertrophy in chronically anemic fetal sheep: increased vascularization is associated with increased myocardial expression of vascular endothelial growth factor and hypoxia-inducible factor 1. Am J Obstet Gynecol 178:527–534
Choudhuri R, Zhang HT, Donnini S et al (1997) An angiogenic role for the neurokines midkine and pleiotrophin in tumorigenesis. Cancer Res 57:1814–1819
Horiba M, Kadomatsu K, Nakamura E et al (2000) Neointima formation in a restenosis model is suppressed in midkine-deficient mice. J Clin Invest 105:489–495
Steffens S, Montecucco F, Mach F (2009) The inflammatory response as a target to reduce myocardial ischaemia and reperfusion injury. Thromb Haemost 102:240–247
Jugdutt BI, Idikio HA (2005) Apoptosis and oncosis in acute coronary syndromes: assessment and implications. Mol Cell Biochem 270:177–200
Herskowitz A, Choi S, Ansari AA et al (1995) Cytokine mRNA expression in postischemic/reperfused myocardium. Am J Pathol 146:419–428
Zhao ZQ, Budde JM, Morris C et al (2001) Adenosine attenuates reperfusion-induced apoptotic cell death by modulating expression of Bcl-2 and Bax proteins. J Mol Cell Cardiol 33:57–68
Baxter GF (2002) The neutrophil as a mediator of myocardial ischemia-reperfusion injury: time to move on. Basic Res Cardiol 97:268–275
Vinten-Johansen J (2004) Involvement of neutrophils in the pathogenesis of lethal myocardial reperfusion injury. Cardiovasc Res 61:481–497
Arras M, Ito WD, Scholz D et al (1998) Monocyte activation in angiogenesis and collateral growth in the rabbit hindlimb. J Clin Invest 101:40–50
Jugdutt BI (2003) Ventricular remodeling after infarction and the extracellular collagen matrix: when is enough enough? Circulation 108:1395–1403
Yoshida S, Yoshida A, Ishibashi T (2004) Induction of IL-8, MCP-1, and bFGF by TNF-alpha in retinal glial cells: implications for retinal neovascularization during post-ischemic inflammation. Graefes Arch Clin Exp Ophthalmol 242:409–413
Power JM, Raman J, Dornom A et al (1999) Passive ventricular constraint amends the course of heart failure: a study in an ovine model of dilated cardiomyopathy. Cardiovasc Res 44:549–555
Harada M, Tsuji Y, Sumida A et al (2009) Midkine prevents cardiac remodeling in rabbit congestive heart failure through its anti-apoptotic effect. Circulation J 73 (Suppl 1):143
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Additional information
Funding: These works were supported by grants from the Ministry of Education, Culture, Sports, Science and technology, Japan.
Conflict of Interest: None.
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media B.V.
About this chapter
Cite this chapter
Horiba, M., Kadomatsu, K. (2012). Midkine and Heart Failure. In: Ergüven, M., Muramatsu, T., Bilir, A. (eds) Midkine: From Embryogenesis to Pathogenesis and Therapy. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4234-5_9
Download citation
DOI: https://doi.org/10.1007/978-94-007-4234-5_9
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-4233-8
Online ISBN: 978-94-007-4234-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)