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Cardiovascular Drugs and Therapy

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01-10-2016 | ORIGINAL ARTICLE

Vasostatin-1 Stops Structural Remodeling and Improves Calcium Handling via the eNOS-NO-PKG Pathway in Rat Hearts Subjected to Chronic β-Adrenergic Receptor Activation

Authors: Dandan Wang, Yingguang Shan, Yan Huang, Yanhong Tang, Yuting Chen, Ran Li, Jing Yang, Congxin Huang

Published in: Cardiovascular Drugs and Therapy | Issue 5/2016

Abstract

Purpose

Chronically elevated catecholamine levels activate cardiac β-adrenergic receptors, which play a vital role in the pathogenesis of heart failure. Evidence suggests that vasostatin-1 (VS-1) exerts anti-adrenergic effects on isolated and perfused hearts in vitro. Whether VS-1 ameliorates hypertrophy/remodeling by inducing the chronic activation of β-adrenergic receptors is unknown. The present study aims to test the efficacy of using VS-1 to treat the advanced hypertrophy/remodeling that result from chronic β-adrenergic receptor activation and to determine the cellular and molecular mechanisms that underlie this response.

Methods and Result

Rats were subjected to infusion with either isoprenaline (ISO, 5 mg/kg/d), ISO plus VS-1 (30 mg/kg/d) or placebo for 2 weeks. VS-1 suppressed chamber dilation, myocyte hypertrophy and fibrosis and improved in vivo heart function in the rats subjected to ISO infusion. VS-1 increased phosphorylated nitric oxide synthase levels and induced the activation of protein kinase G. VS-1 also deactivated multiple hypertrophy signaling pathways that were triggered by the chronic activation of β-adrenergic receptors, such as the phosphoinositide-3 kinase (PI3K)/Akt and Ca²⁺/calmodulin-dependent kinase (CaMK-II) pathways. Myocytes isolated from ISO + VS-1 hearts displayed higher Ca²⁺ transients, shorter Ca²⁺ decays, higher sarcoplasmic reticulum Ca²⁺ levels and higher L-type Ca²⁺ current densities than the ISO rat hearts. VS-1 treatment restored the protein expression of sarcoplasmic reticulum Ca²⁺ uptake ATPase, phospholamban and Cav1.2, indicating improved calcium handling.

Conclusions

Chronic VS-1 treatment inhibited the progression of hypertrophy, fibrosis, and chamber remodeling, and improved cardiac function in a rat model of ISO infusion. In addition, Ca²⁺ handling and its molecular modulation were also improved by VS-1. The beneficial effects of VS-1 on cardiac remodeling may be mediated by the enhanced activation of the eNOS-cGMP-PKG pathway.

Samuels MA. The brain-heart connection. Circulation. 2007;116:77–84.CrossRefPubMed

Goldspink DF, Burniston JG, Ellison GM, Clark WA, Tan LB. Catecholamine-induced apoptosis and necrosis in cardiac and skeletal myocytes of the rat in vivo: the same or separate death pathways? Exp Physiol. 2004;89:407–16.CrossRefPubMed

Chien KR, Knowlton KU, Zhu H, Chien S. Regulation of cardiac gene expression during myocardial growth and hypertrophy: molecular studies of an adaptive physiologic response. FASEB J. 1991;5:3037–46.PubMed

Kitagawa, Y, Yamashita, D, Ito, H and Takaki, M. Reversible effects of isoproterenol-induced hypertrophy on in situ left vetricular function in rat hearts. Am J Physiol Heart Circ Physiol 2004;287:H277-HH85.

Zhang GX, Kimura S, Nishiyama A, Shokoji T, Rahman M, Yao L, et al. Cardiac oxidative stress in acute and chronic isoproterenol-infused rats. Cardiovasc Res. 2005;65:230–8.CrossRefPubMed

Cohn JN, Levine TB, Olivari MT, Gaberg V, Lura D, Francis GS, et al. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med. 1984;311:819–23.CrossRefPubMed

Esler M, Kaye D, Lambert G, Esler D, Jennings G. Adrenergic nervous system in heart failure. Am J Cardiol. 1997;80:7 L–14 L.CrossRef

Mahapatra NR. Catestatin is a novel endogenous peptide that regulates cardiac function and blood pressure. Cardiovasc Res. 2008;80:330–8.CrossRefPubMed

Corti A, Mannarino C, Mazza R, Angelone T, Longhi R, Tota B, Chromogranin AN. Terminal fragments vasostatin-1 and the synthetic CGA 7-57 peptide act as cardiostatins on the isolated working frog heart. Gen Comp Endocrinol. 2004;136:217–24.CrossRefPubMed

10.

Gallo MP, Levi R, Ramella R, Brero A, Boero O, Tota B, et al. Endothelium-derived nitric oxide mediates the antiadrenergic effect of human vasostatin-1 in rat ventricular myocardium. Am J Physiol Heart Circ Physiol. 2007;292:2906–12.CrossRef

11.

Cerra MC, De Iuri L, Angelone T, Corti A, Tota B, Recombinant N. Terminal fragments of chromogranin-a modulate cardiac function of the Langendorff-perfused rat heart. Basic Res Cardiol. 2006;101:43–52.CrossRefPubMed

12.

Cappello S, Angelone T, Tota B, Pagliaro P, Penna C, Rastaldo R, et al. Human recombinant chromogranin A-derived vasostatin-1 mimics preconditioning via an adenosine/nitric oxide signaling mechanism. Am J Physiol Heart Circ Physiol. 2007;293:719–27.CrossRef

13.

Glattard E, Angelone T, Strub JM, Corti A, Aunis D, Tota B, et al. Characterization of natural vasostatin-containing peptides in rat heart. FEBS J. 2006;273:3311–21.CrossRefPubMed

14.

Corti A, Perez Sanchez L, Gasparri A, Curnis F, Longhi R, Branaazza A, et al. Production and structure characterization of recombinant chromograin a N-terminal fragment (vasostatin. Eur J Biochem. 1997;248:692–9.CrossRefPubMed

15.

Huang CX, Yuan MJ, Huang H, Wu G, Liu Y, SB Y, et al. Ghrelin inhibits post-infarct myocardial remodeling and improves cardiac function through anti-inflammation effect. Peptides. 2009;30:2286–91.CrossRefPubMed

16.

Yamamoto K, Dang QN, Kennedy SP, Osathanondh R, Kelly RA, Lee RT. Induction of tenascin-C in cardiac myocytes by mechanical deformation. J Biol Chem. 1999;274:21840–6.CrossRefPubMed

17.

Takinmoto E, Champion HC, Li M, Belardi D, Ren S, Rodriguez ER, et al. Chronic inhibition of cyclic GMP phosphodiesterase 5 A prevents and reverses cardiac hypertrophy. Nat Med. 2005;11:214–22.CrossRef

18.

Liu B, Ho HT, Velez-Cortes F, Lou Q, Valdivia CR, Knollmann BC, et al. Genetic ablation of ryanodine receptor 2 phosphorylation at Ser-2808 aggravates Ca(2+)-dependent cardiomyopathy by exacerbating diastolic Ca2+ release. J Physiol. 2014;592:1957–73.CrossRefPubMedPubMedCentral

19.

Soltysinska E, Olesen SP, Osadchii OE. Myocardial structural, contractile, and electrophysiological changes in the Guinea-pig heart failure model induced by chronic sympathetic activation. Exp Physiol. 2011;96:647–63.CrossRefPubMed

20.

Osadchii OE. Cardiac hypertrophy induced by sustained beta-adrenoreceptor activation: pathophysiological aspects. Heart Fail Rev. 2007;12:66–86.CrossRefPubMed

21.

Naohiro Yano VI, Ting C. Zhao, Andy Tseng, James F. Padbury, and Yi-tang Tseng. A novel signaling pathway for beta-adrenergic receptor-mediated activation of phosphoinositide 3-kinase in H9c2 cardiomyocytes. Am J Physiol Heart Circ Physiol. 2007;293:H385–H93.CrossRefPubMed

22.

Grimm M, Brown JH. Beta-adrenergic receptor signaling in the heart: role of CaMKII. J Mol Cell Cardiol. 2010;48:322–30.CrossRefPubMed

23.

Lincoln T, Potter TC, Vallee L. Willman, David E. Wolfe. Synthesis, binding, release, and metabolism of norepinephrine in normal and transplanted dog hearts. Circ Res. 1965;16:468–81.CrossRef

24.

Bold AJd. Atrial natriuretic factor: A hormone produced by the heart. Science. 1985;230:767–70.CrossRef

25.

Tota B, Angelone T, Mazza R, Cerra M. The chromogranin A-derived vasostatins new players in the endocrine heart. Curr Med Chem. 2008;15:1444–51.CrossRefPubMed

26.

Pieroni, M, Corti, A, Tota, B, Curnis, F, Angelone, T, Colombo, B, Cerra, MC, Bellocci, F, Crea, F and Maseri, A. Myocardial production of chromogranin a in human heart a new regulator of cardiac function. Eur Heart J 2007;28:1117–1127.

27.

Brodde OE. Beta-adrenoceptor blocker treatment and the cardiac beta-adrenoceptor-G-protein(s)-adenylyl cyclase system in chronic heart failure. Naunyn Schmiedeberg's Arch Pharmacol. 2007;374:361–72.CrossRef

28.

Buys ES, Raher MJ, Blake SL, Neilan TG, Graveline AR, Passeri JJ, et al. Cardiomyocyte-restricted restoration of nitric oxide synthase 3 attenuates left ventricular remodeling after chronic pressure overload. Am J Physiol Heart Circ Physiol. 2007;293:H620–H7.CrossRefPubMed

29.

Ichinose F, Bloch KD, JC W, Hataishi R, Aretz HT, Picard MH, et al. Pressure overload-induced LV hypertrophy and dysfunction in mice are exacerbated by congenital NOS3 deficiency. Am J Physiol Heart Circ Physiol. 2004;286:H1070–H5.CrossRefPubMed

30.

Janssens S, Pokreisz P, Schoonjans L, Pellens M, Vermeersch P, Tjwa M, et al. Cardiomyocyte-specific overexpression of nitric oxide synthase 3 improves left ventricular performance and reduces compensatory hypertrophy after myocardial infarction. Circ Res. 2004;94:1256–62.CrossRefPubMed

31.

Ramella R, Boero O, Alloatti G, Angelone T, Levi R, Gallo MP. Vasostatin 1 activates eNOS in endothelial cells through a proteoglycan-dependent mechanism. J Cell Biochem. 2010;110:70–9.PubMed

32.

Cerra MC, Gallo MP, Angelone T, Quintieri AM, Pulera E, Filice E, et al. The homologous rat chromogranin A1-64 (rCGA1-64) modulates myocardial and coronary function in rat heart to counteract adrenergic stimulation indirectly via endothelium-derived nitric oxide. FASEB J. 2008;22:3992–4004.CrossRefPubMed

33.

Morisco C, Zebrowski D, Condorelli G, Tsichlis P, Vatner SF, Sadoshima J. The Akt-glycogen synthase kinase 3beta pathway regulates transcription of atrial natriuretic factor induced by beta-adrenergic receptor stimulation in cardiac myocytes. J Biol Chem. 2000;275:14466–75.CrossRefPubMed

34.

Condorelli G, Drusco A, Stassi G, Bellacosa A, Roncarati R, Iaccarino G, et al. Akt induces enhanced myocardial contractility and cell size in vivo in transgenic mice. Proc Natl Acad Sci U S A. 2002;99:12333–8.CrossRefPubMedPubMedCentral

35.

Matsui T, Li L, JC W, Cook SA, Nagoshi T, Picard MH, et al. Phenotypic spectrum caused by transgenic overexpression of activated Akt in the heart. J Biol Chem. 2002;277:22896–901.CrossRefPubMed

36.

Hsu S, Nagayama T, Koitabashi N, Zhang M, Zhou L, Bedja D, et al. Phosphodiesterase 5 inhibition blocks pressure overload-induced cardiac hypertrophy independent of the calcineurin pathway. Cardiovasc Res. 2009;81:301–9.CrossRefPubMed

37.

Hasenfuss G, Reinecke H, Studer R, Meyer M, Pieske B, Holtz J, et al. Relation between myocardial function and expression of sarcoplasmic reticulum Ca2 + −ATPase in failing and nonfailing human myocardium. Circ Res. 1994;75:434–42.CrossRefPubMed

38.

Nicolaou P, Kranias EG. Role of PP1 in the regulation of Ca cycling in cardiac physiology and pathophysiology. Front Biosci. 2009;14:3571–85.CrossRef

39.

Schwinger RHG, Munch G, Bolck B, Karczewski P, Krause E-G, Erdmann E. Reduced Ca2 + −sensitivity of SERCA2a in failing human myocardium due to reduced serin-16 phospholamban phoshorylation. J Mol Cell Cardiol. 1999;31:479–91.CrossRefPubMed

40.

Chu G, Lester JW, Young KB, Luo W, Zhai J, Kranias EGA. Single site (Ser16) phosphorylation in phospholamban is sufficient in mediating its maximal cardiac responses to β-agonists. J Biol Chem. 2000;275:38938–43.CrossRefPubMed

41.

Bers D. Calcium cycling and signaling in cardiac myocytes. Annu Rev Physiol. 2008;70:23–49.CrossRefPubMed

42.

Ling H, Zhang T, Pereira L, Means CK, Cheng H, Gu Y, et al. Requirement for Ca2+/calmodulin-dependent kinase II in the transition from pressure overload-induced cardiac hypertrophy to heart failure in mice. J Clin Invest. 2009;119:1230–40.CrossRefPubMedPubMedCentral

43.

Heineke J, Molkentin JD. Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat Rev Mol Cell Biol. 2006;7:589–600.CrossRefPubMed

44.

Jiang LH, Gawler DJ, Hodson N, Milligan CJ, Pearson HA, Porter V, et al. Regulation of cloned cardiac L-type calcium channels by cGMP-dependent protein kinase. J Biol Chem. 2000;275:6135–43.CrossRefPubMed

45.

Schroder F, Single L. Type Ca2+ channel regulation by cGMP-dependent protein kinase type I in adult cardiomyocytes from PKG I transgenic mice. Cardiovasc Res. 2003;60:268–77.CrossRefPubMed

46.

Yeves AM, Garciarena CD, Nolly MB, Chiappe de Cingolani GE, Cingolani HE, Ennis IL. Decreased activity of the Na+/H+ exchanger by phosphodiesterase 5 A inhibition is attributed to an increase in protein phosphatase activity. Hypertension. 2010;56:690–5.CrossRefPubMed

47.

Kilic A, Velic A, De Windt LJ, Fabritz L, Voss M, Mitko D, et al. Enhanced activity of the myocardial Na+/H+ exchanger NHE-1 contributes to cardiac remodeling in atrial natriuretic peptide receptor-deficient mice. Circulation. 2005;112:2307–17.CrossRefPubMed

48.

Perez NG, Piaggio MR, Ennis IL, Garciarena CD, Morales C, Escudero EM, et al. Phosphodiesterase 5 A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction. Hypertension. 2007;49:1095–103.CrossRefPubMed

49.

Nagayama T, Hsu S, Zhang M, Koitabashi N, Bedja D, Gabrielson KL, et al. Sildenafil stops progressive chamber, cellular, and molecular remodeling and improves calcium handling and function in hearts with pre-existing advanced hypertrophy caused by pressure overload. J Am Coll Cardiol. 2009;53:207–15.CrossRefPubMedPubMedCentral

50.

Klaiber M, Kruse M, Völker K, Schröter J, Feil R, Freichel M, et al. Novel insights into the mechanisms mediating the local antihypertrophic effects of cardiac atrial natriuretic peptide: role of cGMP-dependent protein kinase and RGS2. Basic Res Cardiol. 2010;105:583–95.CrossRefPubMedPubMedCentral

51.

Kilic A, Bubikat A, Gassner B, Baba HA, Kuhn M. Local actions of atrial natriuretic peptide counteract angiotensin II stimulated cardiac remodeling. Endocrinology. 2007;148:4162–9.CrossRefPubMed

Title: Vasostatin-1 Stops Structural Remodeling and Improves Calcium Handling via the eNOS-NO-PKG Pathway in Rat Hearts Subjected to Chronic β-Adrenergic Receptor Activation
Authors: Dandan Wang
Yingguang Shan
Yan Huang
Yanhong Tang
Yuting Chen
Ran Li
Jing Yang
Congxin Huang
Publication date: 01-10-2016
Publisher: Springer US
Published in: Cardiovascular Drugs and Therapy / Issue 5/2016
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI: https://doi.org/10.1007/s10557-016-6687-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Vasostatin-1 Stops Structural Remodeling and Improves Calcium Handling via the eNOS-NO-PKG Pathway in Rat Hearts Subjected to Chronic β-Adrenergic Receptor Activation

Abstract

Purpose

Methods and Result

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods and Result

Conclusions

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