nach oben

Erschienen in:

01.09.2014 | Original Article

Cardioprotective effects of adipokine apelin on myocardial infarction

verfasst von: Bao-Hai Zhang, Cai-Xia Guo, Hong-Xia Wang, Ling-Qiao Lu, Ya-Jie Wang, Li-Ke Zhang, Feng-He Du, Xiang-Jun Zeng

Erschienen in: Heart and Vessels | Ausgabe 5/2014

Einloggen, um Zugang zu erhalten

Abstract

Angiogenesis plays an important role in myocardial infarction. Apelin and its natural receptor (angiotensin II receptor-like 1, AGTRL-1 or APLNR) induce sprouting of endothelial cells in an autocrine or paracrine manner. The aim of this study is to investigate whether apelin can improve the cardiac function after myocardial infarction by increasing angiogenesis in infarcted myocardium. Left ventricular end-diastolic pressure (LVEDP), left ventricular end systolic pressure (LVESP), left ventricular developed pressure (LVDP), maximal left ventricular pressure development (±LVdp/dtmax), infarct size, and angiogenesis were evaluated to analyze the cardioprotective effects of apelin on ischemic myocardium. Assays of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, 5-bromo-2′-deoxyuridine incorporation, wound healing, transwells, and tube formation were used to detect the effects of apelin on proliferation, migration, and chemotaxis of cardiac microvascular endothelial cells. Fluorescein isothiocyanate-labeled bovine serum albumin penetrating through monolayered cardiac microvascular endothelial cells was measured to evaluate the effects of apelin on permeability of microvascular endothelial cells. In vivo results showed that apelin increased ±LV dp/dtmax and LVESP values, decreased LVEDP values (all p < 0.05), and promoted angiogenesis in rat heart after ligation of the left anterior descending coronary artery. In vitro results showed that apelin dose-dependently enhanced proliferation, migration, chemotaxis, and tube formation, but not permeability of cardiac microvascular endothelial cells. Apelin also increased the expression of vascular endothelial growth factor receptors-2 (VEGFR2) and the endothelium-specific receptor tyrosine kinase (Tie-2) in cardiac microvascular endothelial cells. These results indicated that apelin played a protective role in myocardial infarction through promoting angiogenesis and decreasing permeability of microvascular endothelial cells via upregulating the expression of VEGFR2 and Tie-2 in cardiac microvascular endothelial cells.

Iribarren C, Phelps BH, Darbinian JA, McCluskey ER, Quesenberry CP, Hytopoulos E, Vogelman JH, Orentreich N (2011) Circulating angiopoietins-1 and -2, angiopoietin receptor Tie-2 and vascular endothelial growth factor-A as biomarkers of acute myocardial infarction: a prospective nested case-control study. BMC Cardiovasc Disord 11:31PubMedCrossRefPubMedCentral

Josko J, Gwozdz B, Jedrzejowska-Szypulka H, Hendryk S (2000) Vascular endothelial growth factor (VEGF) and its effect on angiogenesis. Med Sci Monit 6:1047–1052PubMed

Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407:249–257PubMedCrossRef

Risau W (1997) Mechanisms of angiogenesis. Nature 386:671–674PubMedCrossRef

Tatemoto K, Hosoya M, Habata Y, Fujii R, Kakegawa T, Zou MX, Kawamata Y, Fukusumi S, Hinuma S, Kitada C, Kurokawa T, Onda H, Fujino M (1998) Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun 251:471–476PubMedCrossRef

Devic E, Rizzoti K, Bodin S, Knibiehler B, Audigier Y (1999) Amino acid sequence and embryonic expression of msr/apj, the mouse homolog of Xenopus X-msr and human APJ. Mech Dev 84:199–203PubMedCrossRef

Kleinz MJ, Davenport AP (2004) Immunocytochemical localization of the endogenous vasoactive peptide apelin to human vascular and endocardial endothelial cells. Regul Pept 118:119–125PubMedCrossRef

Szokodi I, Tavi P, Foldes G, Voutilainen-Myllyla S, Ilves M, Tokola H, Pikkarainen S, Piuhola J, Rysa J, Toth M, Ruskoaho H (2002) Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility. Circ Res 91:434–440PubMedCrossRef

Ronkainen VP, Ronkainen JJ, Hanninen SL, Leskinen H, Ruas JL, Pereira T, Poellinger L, Vuolteenaho O, Tavi P (2007) Hypoxia inducible factor regulates the cardiac expression and secretion of apelin. FASEB J 21:1821–1830PubMedCrossRef

10.

Cox CM, D’Agostino SL, Miller MK, Heimark RL, Krieg PA (2006) Apelin, the ligand for the endothelial G-protein-coupled receptor, APJ, is a potent angiogenic factor required for normal vascular development of the frog embryo. Dev Biol 296:177–189PubMedCrossRef

11.

Li F, Li L, Qin X, Pan W, Feng F, Chen F, Zhu B, Liao D, Tanowitz H, Albanese C, Chen L (2008) Apelin-induced vascular smooth muscle cell proliferation: the regulation of cyclin D1. Front Biosci 13:3786–3792PubMedCrossRef

12.

Kasai A, Shintani N, Oda M, Kakuda M, Hashimoto H, Matsuda T, Hinuma S, Baba A (2004) Apelin is a novel angiogenic factor in retinal endothelial cells. Biochem Biophys Res Commun 325:395–400PubMedCrossRef

13.

Carmeliet P (2000) Mechanisms of angiogenesis and arteriogenesis. Nat Med 6:389–395PubMedCrossRef

14.

Zeng XJ, Zhang LK, Wang HX, Lu LQ, Ma LQ, Tang CS (2009) Apelin protects heart against ischemia/reperfusion injury in rat. Peptides 30:1144–1152PubMedCrossRef

15.

Jia YX, Pan CS, Zhang J, Geng B, Zhao J, Gerns H, Yang J, Chang JK, Tang CS, Qi YF (2006) Apelin protects myocardial injury induced by isoproterenol in rats. Regul Pept 133:147–154PubMedCrossRef

16.

Kleinz MJ, Baxter GF (2008) Apelin reduces myocardial reperfusion injury independently of PI3K/Akt and P70S6 kinase. Regul Pept 146:271–277PubMedCrossRef

17.

Simpkin JC, Yellon DM, Davidson SM, Lim SY, Wynne AM, Smith CC (2007) Apelin-13 and apelin-36 exhibit direct cardioprotective activity against ischemia-reperfusion injury. Basic Res Cardiol 102:518–528PubMedCrossRef

18.

Smith CC, Mocanu MM, Bowen J, Wynne AM, Simpkin JC, Dixon RA, Cooper MB, Yellon DM (2007) Temporal changes in myocardial salvage kinases during reperfusion following ischemia: studies involving the cardioprotective adipocytokine apelin. Cardiovasc Drugs Ther 21:409–414PubMedCrossRef

19.

Petrova TV, Makinen T, Alitalo K (1999) Signaling via vascular endothelial growth factor receptors. Exp Cell Res 253:117–130PubMedCrossRef

20.

Davis S, Aldrich TH, Jones PF, Acheson A, Compton DL, Jain V, Ryan TE, Bruno J, Radziejewski C, Maisonpierre PC, Yancopoulos GD (1996) Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell 87:1161–1169PubMedCrossRef

21.

Dumont DJ, Gradwohl G, Fong GH, Puri MC, Gertsenstein M, Auerbach A, Breitman ML (1994) Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal a critical role in vasculogenesis of the embryo. Genes Dev 8:1897–1909PubMedCrossRef

22.

Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN, Yancopoulos GD (1996) Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 87:1171–1180PubMedCrossRef

23.

Yu GG, Zeng XJ, Wang HX, Lu LQ, Zheng SP, Ma LQ, Chang J, Wang J, Zhang DM, Du FH, Zhang LK (2011) Cytochrome P450 2J3/epoxyeicosatrienoic acids mediate the cardioprotection induced by ischaemic post-conditioning, but not preconditioning, in the rat. Clin Exp Pharmacol Physiol 38:63–70PubMedCrossRef

24.

Yang JJ, Liu ZQ, Zhang JM, Wang HB, Hu SY, Liu JF, Wang CY, Chen YD (2013) Real-time tracking of adipose tissue-derived stem cells with injectable scaffolds in the infarcted heart. Heart Vessels 28:385–396PubMedCrossRef

25.

Pfeffer JM, Pfeffer MA, Fletcher PJ, Braunwald E (1991) Progressive ventricular remodeling in rat with myocardial infarction. Am J Physiol 260:H1406–H1414PubMed

26.

Yang JP, Liu HJ, Liu XF (2010) VEGF promotes angiogenesis and functional recovery in stroke rats. J Invest Surg 23:149–155PubMedCrossRef

27.

Moccia F, Baruffi S, Spaggiari S, Coltrini D, Berra-Romani R, Signorelli S, Castelli L, Taglietti V, Tanzi F (2001) P2y1 and P2y2 receptor-operated Ca2+ signals in primary cultures of cardiac microvascular endothelial cells. Microvasc Res 61:240–252PubMedCrossRef

28.

Nishida M, Carley WW, Gerritsen ME, Ellingsen O, Kelly RA, Smith TW (1993) Isolation and characterization of human and rat cardiac microvascular endothelial cells. Am J Physiol 264:H639–H652PubMed

29.

Zeng R, Chen YC, Zeng Z, Liu XX, Liu R, Qiang O, Li X (2012) Inhibition of mini-TyrRS-induced angiogenesis response in endothelial cells by VE-cadherin-dependent mini-TrpRS. Heart Vessels 27:193–201PubMedCrossRef

30.

Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J (2000) Vascular-specific growth factors and blood vessel formation. Nature 407:242–248PubMedCrossRef

31.

Li ZD, Bork JP, Krueger B, Patsenker E, Schulze-Krebs A, Hahn EG, Schuppan D (2005) VEGF induces proliferation, migration, and TGF-beta1 expression in mouse glomerular endothelial cells via mitogen-activated protein kinase and phosphatidylinositol 3-kinase. Biochem Biophys Res Commun 334:1049–1060PubMedCrossRef

32.

Giurdanella G, Motta C, Muriana S, Arena V, Anfuso CD, Lupo G, Alberghina M (2011) Cytosolic and calcium-independent phospholipase A(2) mediate glioma-enhanced proangiogenic activity of brain endothelial cells. Microvasc Res 81:1–17PubMedCrossRef

33.

Fox SB, Leek RD, Weekes MP, Whitehouse RM, Gatter KC, Harris AL (1995) Quantitation and prognostic value of breast cancer angiogenesis: comparison of microvessel density, Chalkley count, and computer image analysis. J Pathol 177:275–283PubMedCrossRef

34.

Van Nieuw Amerongen GP, Van Hinsbergh VW (1999) Determination of the endothelial barrier function in vitro. Methods Mol Biol 96:183–189PubMed

35.

Magrane J, Christensen RA, Rosen KM, Veereshwarayya V, Querfurth HW (2006) Dissociation of ERK and Akt signaling in endothelial cell angiogenic responses to beta-amyloid. Exp Cell Res 312:996–1010PubMedCrossRef

36.

Kidoya H, Naito H, Takakura N (2010) Apelin induces enlarged and nonleaky blood vessels for functional recovery from ischemia. Blood 115:3166–3174PubMedCrossRef

37.

Kadoglou NP, Lampropoulos S, Kapelouzou A, Gkontopoulos A, Theofilogiannakos EK, Fotiadis G, Kottas G (2010) Serum levels of apelin and ghrelin in patients with acute coronary syndromes and established coronary artery disease—KOZANI Study. Transl Res 155:238–246PubMedCrossRef

38.

Rastaldo R, Cappello S, Folino A, Berta GN, Sprio AE, Losano G, Samaja M, Pagliaro P (2011) Apelin-13 limits infarct size and improves cardiac postischemic mechanical recovery only if given after ischemia. Am J Physiol Heart Circ Physiol 300:H2308–H2315PubMedCrossRef

39.

Kjekshus J (1987) Nitrates in acute myocardial infarction. Drugs 33(Suppl 4):140–146PubMedCrossRef

40.

Segers VF, Lee RT (2010) Protein therapeutics for cardiac regeneration after myocardial infarction. J Cardiovasc Transl Res 3:469–477PubMedCrossRefPubMedCentral

41.

Mehlhorn U, Geissler HJ, Laine GA, Allen SJ (2001) Myocardial fluid balance. Eur J Cardiothorac Surg 20:1220–1230PubMedCrossRef

42.

Frangogiannis NG (2012) Regulation of the inflammatory response in cardiac repair. Circ Res 110:159–173PubMedCrossRefPubMedCentral

43.

Kasseckert SA, Schafer C, Kluger A, Gligorievski D, Tillmann J, Schluter KD, Noll T, Sauer H, Piper HM, Abdallah Y (2009) Stimulation of cGMP signalling protects coronary endothelium against reperfusion-induced intercellular gap formation. Cardiovasc Res 83:381–387PubMedCrossRef

44.

Thurston G, Rudge JS, Ioffe E, Zhou H, Ross L, Croll SD, Glazer N, Holash J, McDonald DM, Yancopoulos GD (2000) Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med 6:460–463PubMedCrossRef

45.

Ward NL, Dumont DJ (2002) The angiopoietins and Tie2/Tek: adding to the complexity of cardiovascular development. Semin Cell Dev Biol 13:19–27PubMedCrossRef

Titel: Cardioprotective effects of adipokine apelin on myocardial infarction
verfasst von: Bao-Hai Zhang
Cai-Xia Guo
Hong-Xia Wang
Ling-Qiao Lu
Ya-Jie Wang
Li-Ke Zhang
Feng-He Du
Xiang-Jun Zeng
Publikationsdatum: 01.09.2014
Verlag: Springer Japan
Erschienen in: Heart and Vessels / Ausgabe 5/2014
Print ISSN: 0910-8327
Elektronische ISSN: 1615-2573
DOI: https://doi.org/10.1007/s00380-013-0425-z

Neu im Fachgebiet Kardiologie

Screening-Mammografie offenbart erhöhtes Herz-Kreislauf-Risiko

26.04.2024 Mammografie Nachrichten

Routinemäßige Mammografien helfen, Brustkrebs frühzeitig zu erkennen. Anhand der Röntgenuntersuchung lassen sich aber auch kardiovaskuläre Risikopatientinnen identifizieren. Als zuverlässiger Anhaltspunkt gilt die Verkalkung der Brustarterien.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Adipositas-Medikament auch gegen Schlafapnoe wirksam

24.04.2024 Adipositas Nachrichten

Der als Antidiabetikum sowie zum Gewichtsmanagement zugelassene Wirkstoff Tirzepatid hat in Studien bei adipösen Patienten auch schlafbezogene Atmungsstörungen deutlich reduziert, informiert der Hersteller in einer Vorab-Meldung zum Studienausgang.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2014

Efficacy and safety of aspirin, clopidogrel, and warfarin after coronary artery stenting in Korean patients with atrial fibrillation

Gender differences in factors influencing electrocardiographic findings of left ventricular hypertrophy in severe aortic stenosis

Pentraxin 3 is a local inflammatory marker in atrial fibrillation

Pseudo-postpacing interval of diastolic potential after entrainment pacing of remote bystander pathway in reentrant ventricular tachycardia