Top

Published in:

Open Access 01-12-2012 | Original investigation

Regional evidence of modulation of cardiac adiponectin level in dilated cardiomyopathy: pilot study in a porcine animal model

Authors: Chiara Caselli, Vincenzo Lionetti, Manuela Cabiati, Tommaso Prescimone, Giovanni D Aquaro, Virginia Ottaviano, Fabio Bernini, Letizia Mattii, Silvia Del Ry, Daniela Giannessi

Published in: Cardiovascular Diabetology | Issue 1/2012

Abstract

Background

The role of systemic and myocardial adiponectin (ADN) in dilated cardiomyopathy is still debated. We tested the regulation of both systemic and myocardial ADN and the relationship with AMP-activated protein kinase (AMPK) activity in a swine model of non-ischemic dilated cardiomyopathy.

Methods and results

Cardiac tissue was collected from seven instrumented adult male minipigs by pacing the left ventricular (LV) free wall (180 beats/min, 3 weeks), both from pacing (PS) and opposite sites (OS), and from five controls. Circulating ADN levels were inversely related to global and regional cardiac function. Myocardial ADN in PS was down-regulated compared to control (p < 0.05), yet ADN receptor 1 was significantly up-regulated (p < 0.05). No modifications of AMPK were observed in either region of the failing heart. Similarly, myocardial mRNA levels of PPARγ, PPARα, TNFα, iNOS were unchanged compared to controls.

Conclusions

Paradoxically, circulating ADN did not show any cardioprotective effect, confirming its role as negative prognostic biomarker of heart failure. Myocardial ADN was reduced in PS compared to control in an AMPK-independent fashion, suggesting the occurrence of novel mechanisms by which reduced cardiac ADN levels may regionally mediate the decline of cardiac function.

Available only for authorised users

Ouchi N, Walsh K: Adiponectin as an anti-inflammatory factor. Clin Chem Acta. 2007, 380: 24-30. 10.1016/j.cca.2007.01.026.CrossRef

Ding G, Qin Q, He N, Francis-David SC, Hou J, Liu J, Ricks E, Yang Q: Adiponectin and its receptors are expressed in adult ventricular cardiomyocytes and upregulated by activation of peroxisome proliferator-activated receptor gamma. J Mol Cell Cardiol. 2007, 43: 73-84. 10.1016/j.yjmcc.2007.04.014.PubMedCentralCrossRefPubMed

Cao Y, Tao L, Yuan Y, Jiao X, Lau WB, Wang Y, Christopher T, Lopez B, Chan L, Goldstein B, Ma XL: Endothelial dysfunction in adiponectin deficiency and its mechanisms involved. J Mol Cell Cardiol. 2009, 46: 413-419. 10.1016/j.yjmcc.2008.10.014.PubMedCentralCrossRefPubMed

Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Christopher T, Lopez B, Chan L, Goldstein B, Ma XL: Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003, 423: 762-769. 10.1038/nature01705.CrossRefPubMed

Denzel MS, Scimia MC, Zumstein PM, Walsh K, Ruiz-Lozano P, Ranscht B: T-cadherin is critical for adiponectin-mediated cardioprotection in mice. J Clin Invest. 2010, 120: 4342-4352. 10.1172/JCI43464.PubMedCentralCrossRefPubMed

Lionetti V, Stanley WC, Recchia FA: Modulating fatty acid oxidation in heart failure. Cardiovasc Res. 2011, 90: 202-209. 10.1093/cvr/cvr038.PubMedCentralCrossRefPubMed

Kadowaki T, Yamauchi T: Adiponectin and adiponectin receptors. Endocr Rev. 2005, 26: 439-451. 10.1210/er.2005-0005.CrossRefPubMed

Katagiri H, Yamada T, Oka Y: Adiposity and cardiovascular disorders: disturbance of the regulatory system consisting of humoral and neuronal signals. Cir Res. 2007, 101: 27-39. 10.1161/CIRCRESAHA.107.151621.CrossRef

Shibata R, Sato K, Pimentel DR, Takemura Y, Kihara S, Ohashi K, Funahashi T, Ouchi N, Walsh K: Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanism. Nat Med. 2005, 11: 1096-1103. 10.1038/nm1295.PubMedCentralCrossRefPubMed

10.

Giannessi D, Maltinti M, Del Ry S: Adiponectin circulating levels: a new emerging biomarker of cardiovascular risk. Pharmacol Res. 2007, 56: 459-467. 10.1016/j.phrs.2007.09.014.CrossRefPubMed

11.

Goldstein BJ, Scalia RG, Ma XL: Protective vascular and myocardial effects of adiponectin. Nat Clin Pract Cardiovasc Med. 2009, 6: 27-35. 10.1038/ncpcardio1398.PubMedCentralCrossRefPubMed

12.

Kumada M, Kihara S, Sumitsuji S, Kawamoto T, Matsumoto S, Ouchi N, Arita Y, Okamoto Y, Shimomura I, Hiraoka H, Nakamura T, Funahashi T, Matsuzawa Y, Osaka CAD Study Group: Coronary artery disease. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol. 2003, 23: 85-89. 10.1161/01.ATV.0000048856.22331.50.CrossRefPubMed

13.

Nakamura Y, Shimada K, Fukuda D, Shimada Y, Ehara S, Hirose M, Kataoka T, Kamimori K, Shimodozono S, Kobayashi Y, Yoshiyama M, Takeuchi K, Yoshikawa J: Implications of plasma concentrations of adiponectin in patients with coronary artery disease. Heart. 2004, 90: 528-533. 10.1136/hrt.2003.011114.PubMedCentralCrossRefPubMed

14.

Maahs DM, Ogden LG, Kinney GL, Wadwa P, Snell-Bergeon JK, Dabelea D, Hokanson JE, Ehrlich J, Eckel RH, Rewers M: Low plasma adiponectin levels predict progression of coronary artery calcification. Circulation. 2005, 111: 747-753. 10.1161/01.CIR.0000155251.03724.A5.CrossRefPubMed

15.

von Eynatten M, Humpert PM, Bluemm A, Lepper PM, Hamann A, Allolio B, Nawroth PP, Bierhaus A, Dugi KA: High-molecular weight adiponectin is independently associated with the extent of coronary artery disease in men. Atherosclerosis. 2008, 199: 123-128. 10.1016/j.atherosclerosis.2007.10.002.CrossRefPubMed

16.

Kollias A, Tsiotra PC, Ikonomidis I, Maratou E, Mitrou P, Kyriazi E, Boutati E, Lekakis J, Economopoulos T, Kremastinos DT, Dimitriadis G, Raptis SA: Adiponectin levels and expression of adiponectin receptors in isolated monocytes from overweight patients with coronary artery disease. Cardiovasc Diabetol. 2011, 1: 10-14.

17.

Chen WJ, Rijzewijk LJ, van der Meer RW, Heymans MW, van Duinkerken E, Lubberink M, Lammertsma AA, Lamb HJ, de Roos A, Romijn JA, Smit JW, Bax JJ, Bjerre M, Frystyk J, Flyvbjerg A, Diamant M: Association of plasma osteoprotegerin and adiponectin with arterial function, cardiac function and metabolism in asymptomatic type 2 diabetic men. Cardiovasc Diabetol. 2011, 19: 10-67.

18.

Giannessi D, Caselli C, Del Ry S, Maltinti M, Pardini S, Turchi S, Cabiati M, Sampietro T, Abraham N, L'abbate A, Neglia D: Adiponectin is associated with abnormal lipid profile and coronary microvascular dysfunction in patients with dilated cardiomyopathy without overt heart failure. Metabolism. 2011, 60: 227-233. 10.1016/j.metabol.2009.12.030.PubMedCentralCrossRefPubMed

19.

Tsutamoto T, Tanaka T, Sakai H, Ishikawa C, Fujii M, Yamamoto T, Horie M: Total and high molecular weight adiponectin, haemodynamics, and mortality in patients with chronic heart failure. Eur Heart J. 2007, 28: 1723-1730. 10.1093/eurheartj/ehm154.CrossRefPubMed

20.

Kistorp C, Faber J, Galatius S, Gustafsson F, Frysryk J, Flyvbjerg A, Hildebrandt P: Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure. Circulation. 2005, 112: 1756-1762. 10.1161/CIRCULATIONAHA.104.530972.CrossRefPubMed

21.

Kintscher U: Does adiponectin resistance exist in chronic heart failure?. Eur Heart J. 2007, 28: 1676-1677. 10.1093/eurheartj/ehm233.CrossRefPubMed

22.

Lionetti V, Guiducci L, Simioniuc A, Aquaro GD, Simi C, De Marchi D, Burchielli S, Pratali L, Piacenti M, Lombardi M, Salvadori P, Pingitore A, Neglia D, Recchia FA: Mismatch between uniform increase in cardiac glucose uptake and regional contractile dysfunction in pacing-induced heart failure. Am J Physiol Heart Circ Physiol. 2007, 293: 2747-2756. 10.1152/ajpheart.00592.2007.CrossRef

23.

Lionetti V, Aquaro GD, Simioniuc A, Di Cristofano C, Forini F, Cecchetti F, Campan M, De Marchi D, Bernini F, Grana M, Nannipieri M, Mancini M, Lombardi M, Recchia FA, Pingitore A: Severe mechanical dyssynchrony causes regional hibernation-like changes in pigs with nonischemic heart failure. J Card Fail. 2009, 15: 920-928. 10.1016/j.cardfail.2009.06.436.CrossRefPubMed

24.

Prinzen FW, Hunter WC, Wyman BT, McVeigh ER: Mapping of regional myocardial strain and work during ventricular pacing: experimental study using magnetic resonance imaging tagging. J Am Coll Cardiol. 1999, 33: 1735-1742. 10.1016/S0735-1097(99)00068-6.PubMedCentralCrossRefPubMed

25.

Del Ry S, Cabiati M, Lionetti V, Simioniuc A, Caselli C, Prescimone T, Emdin M, Giannessi D: Asymmetrical myocardial expression of natriuretic peptides in pacing-induced heart failure. Peptides. 2009, 30: 1710-1713. 10.1016/j.peptides.2009.06.013.CrossRefPubMed

26.

Martino A, Cabiati M, Campan M, Prescimone T, Minocci D, Caselli C, Rossi AM, Giannessi D, Del Ry S: Selection of reference genes for normalization of real time PCR data in minipig heart failure model and evaluation of TNF alpha mRNA expression. J Biotechnol. 2011, 153: 92-99. 10.1016/j.jbiotec.2011.04.002.CrossRefPubMed

27.

Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F: Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002, 3: RESEARCH0034.PubMedCentralCrossRefPubMed

28.

Takano H, Obata J, Kodama Y, Kitta Y, Nakamura T, Mende A, Kawabata K, Saito Y, Fujioka D, Kobayashi T, Yano T, Sano K, Kugiyama K: Adiponectin is released from the heart in patients with heart failure. Int J Cardiol. 2009, 20: 221-226.CrossRef

29.

Tsukamoto O, Fujita M, Kato M, Yamazaki S, Asano Y, Ogai A, Okazaki H, Asai M, Nagamachi Y, Maeda N, Shintani Y, Minamino T, Asakura M, Kishimoto I, Funahashi T, Tomoike H, Kitakaze M: Natriuretic peptides enhance the production of adiponectin in human adipocytes and in patients with chronic heart failure. J Am Coll Cardiol. 2009, 53: 2070-2077. 10.1016/j.jacc.2009.02.038.CrossRefPubMed

30.

Tanaka K, Tsutamoto T, Sakai H, Nishivama K, Fujii M, Yamamoto T, Horie M: Effect of atrial natriuretic peptide on adiponectin in patients with heart failure. Eur J Heart Fail. 2008, 10: 360-366. 10.1016/j.ejheart.2008.02.005.CrossRefPubMed

31.

Stanek B, Frey B, Hülsmann M, Berger R, Sturm B, Strametz-Juranek J, Bergler-Klein J, Moser P, Bojic A, Hartter E, Pacher R: Prognostic evaluation of neurohumoral plasma levels before and during beta-blocker therapy in advanced left ventricular dysfunction. J Am Coll Cardiol. 2001, 38: 436-442. 10.1016/S0735-1097(01)01383-3.CrossRefPubMed

32.

McEntegart MB, Awede B, Petrie MC, Sattar N, Dunn FG, MacFarlane NG, McMurray JJ: Increase in serum adiponectin concentration in patients with heart failure and cachexia: relationship with leptin, other cytokines, and B-type natriuretic peptide. Eur Heart J. 2007, 28: 829-835. 10.1093/eurheartj/ehm033.CrossRefPubMed

33.

Lau CH, Muniandy S: Novel adiponectin-resistin (AR) and insulin resistance (IRAR) indexes are useful integrated diagnostic biomarkers for insulin resistance, type 2 diabetes and metabolic syndrome: a case control study. Cardiovasc Diabetol. 2011, 21 (10(1)): 8.CrossRef

34.

Mamas MA, Deaton C, Rutter MK, Yuille M, Williams SG, Ray SG, New J, Gibson JM, Neyses L: Impaired glucose tolerance and insulin resistance in heart failure: under-recognized and under-treated?. J Card Fail. 2010, 16: 761-768. 10.1016/j.cardfail.2010.05.027.CrossRefPubMed

35.

Van Berendoncks AM, Garnier A, Beckers P, Hoymans VY, Possemiers N, Fortin D, Martinet W, Van Hoof V, Vrints CJ, Ventura-Clapier R, Conraads VM: Functional adiponectin resistance at the level of the skeletal muscle in mild to moderate chronic heart failure. Circ Heart Fail. 2010, 3: 185-194. 10.1161/CIRCHEARTFAILURE.109.885525.CrossRefPubMed

36.

Skurk C, Wittchen F, Suckau L, Witt H, Noutsias M, Fechner H, Schultheiss HP, Poller W: Description of a local cardiac adiponectin system and its deregulation in dilated cardiomyopathy. Eur Heart J. 2008, 29: 1168-1180. 10.1093/eurheartj/ehn136.CrossRefPubMed

37.

Wittchen F, Suckau L, Witt H, Skurk C, Lassner D, Fechner H, Sipo I, Ungethüm U, Ruiz P, Pauschinger M, Tschope C, Rauch U, Kühl U, Schultheiss HP, Poller W: Genomic expression profiling of human inflammatory cardiomyopathy (DCMi) suggests novel therapeutic targets. J Mol Med. 2007, 85: 257-271. 10.1007/s00109-006-0122-9.PubMedCentralCrossRefPubMed

38.

Liao Y, Xuan W, Zhao J, Bin J, Zhao H, Asakura M, Funahashi T, Takashima S, Kitakaze M: Antihypertrophic effects of adiponectin on cardiomyocytes are associated with the inhibition of heparin-binding epidermal growth factor signaling. Bioch Biophy Res Com. 2010, 393: 519-525. 10.1016/j.bbrc.2010.02.039.CrossRef

39.

Shibata R, Izumiya Y, Sato K, Papanicolaou K, Kihara S, Colucci WS, Sam F, Ouchi N, Walsh K: Adiponectin protects against the development of systolic dysfunction following myocardial infarction. J Mol Cell Cardiol. 2007, 42: 1065-1074. 10.1016/j.yjmcc.2007.03.808.PubMedCentralCrossRefPubMed

40.

Kondo K, Shibata R, Unno K, Shimano M, Ishii M, Kito T, Shintani S, Walsh K, Ouchi N, Murohara T: Impact of a single intracoronary administration of adiponectin on myocardial ischemia/reperfusion injury in a pig model. Circ Cardiovasc Interv. 2010, 3: 166-173. 10.1161/CIRCINTERVENTIONS.109.872044.PubMedCentralCrossRefPubMed

41.

Okamoto Y, Arita Y, Nishida M, Muraguchi M, Ouchi N, Takahashi M, Igura T, Inui Y, Kihara S, Nakamura T, Yamashita S, Miyagawa J, Funahashi T, Matsuzawa Y: An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls. Horm Metab Res. 2000, 32: 47-50. 10.1055/s-2007-978586.CrossRefPubMed

42.

Li R, Wang WQ, Zhang H, Yang X, Fan Q, Christopher TA, Lopez BL, Tao L, Goldstein BJ, Gao F, Ma XL: Reduced vascular responsiveness to adiponectin in hyperlipidemic rats–mechanisms and significance. J Mol Cell Cardiol. 2010, 49: 508-515. 10.1016/j.yjmcc.2010.03.002.PubMedCentralCrossRefPubMed

43.

Liu S, Yin T, Wei X, Yi W, Qu Y, Liu Y, Wang R, Lian K, Xia C, Pei H, Sun L, Ma Y, Lau WB, Gao E, Koch WJ, Wang H, Tao L: Downregulation of adiponectin induced by tumor necrosis factor α is involved in the aggravation of posttraumatic myocardial ischemia/reperfusion injury. Crit Care Med. 2011, 39: 1935-1943. 10.1097/CCM.0b013e31821b85db.CrossRefPubMed

44.

Sen B, Xie Z, Case N, Ma M, Rubin C, Rubin J: Mechanical strain inhibits adipogenesis in mesenchymal stem cells by stimulating a durable beta-catenin signal. Endocrinology. 2008, 149: 6065-6075. 10.1210/en.2008-0687.PubMedCentralCrossRefPubMed

45.

Wang Y, Gao E, Tao L, Lau WB, Yuan Y, Goldstein BJ, Lopez BL, Christopher TA, Tian R, Koch W, Ma XL: AMP-activated protein kinase deficiency enhances myocardial ischemia/reperfusion injury but has minimal effect on the antioxidant/antinitrative protection of adiponectin. Circulation. 2009, 119: 835-844. 10.1161/CIRCULATIONAHA.108.815043.PubMedCentralCrossRefPubMed

46.

Ikeda Y, Ohashi K, Shibata R, Pimentel DR, Kihara S, Ouchi N, Walsh K: Cyclooxygenase-2 induction by adiponectin is regulated by a sphingosine kinase-1 dependent mechanism in cardiac myocytes. FEBS Lett. 2008, 582: 1147-1150. 10.1016/j.febslet.2008.03.002.PubMedCentralCrossRefPubMed

47.

Holland WL, Miller RA, Wang ZV, Sun K, Barth BM, Bui HH, Davis KE, Bikman BT, Halberg N, Rutkowski JM, Wade MR, Tenorio VM, Kuo MS, Brozinick JT, Zhang BB, Birnbaum MJ, Summers SA, Scherer PE: Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nat Med. 2011, 17: 55-63. 10.1038/nm.2277.PubMedCentralCrossRefPubMed

48.

Kadowaki T, Yamauchi T: Adiponectin receptor signaling: a new layer to the current model. Cell Metab. 2011, 13: 123-124. 10.1016/j.cmet.2011.01.012.CrossRefPubMed

49.

Beauloye C, Bertrand L, Horman S, Hue L: AMPK activation, a preventive therapeutic target in the transition from cardiac injury to heart failure. Cardiovasc Res. 2011, 90: 224-233. 10.1093/cvr/cvr034.CrossRefPubMed

50.

Towler MC, Hardie DG: AMP-activated protein kinase in metabolic control and insulin signaling. Circ Res. 2007, 16: 328-341.CrossRef

51.

Dixon JA, Spinale FG: Large animal models of heart failure: a critical link in the translation of basic science to clinical practice. Circ Heart Fail. 2009, 2: 262-271. 10.1161/CIRCHEARTFAILURE.108.814459.PubMedCentralCrossRefPubMed

Title: Regional evidence of modulation of cardiac adiponectin level in dilated cardiomyopathy: pilot study in a porcine animal model
Authors: Chiara Caselli
Vincenzo Lionetti
Manuela Cabiati
Tommaso Prescimone
Giovanni D Aquaro
Virginia Ottaviano
Fabio Bernini
Letizia Mattii
Silvia Del Ry
Daniela Giannessi
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Cardiovascular Diabetology / Issue 1/2012
Electronic ISSN: 1475-2840
DOI: https://doi.org/10.1186/1475-2840-11-143

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Regional evidence of modulation of cardiac adiponectin level in dilated cardiomyopathy: pilot study in a porcine animal model

Abstract

Background

Methods and results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods and results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2012

Adipocytokine levels mark endothelial function in normotensive individuals

Angiotensin II type 1 and type 2 receptor expression in circulating monocytes of diabetic and hypercholesterolemic patients over 3-month rosuvastatin treatment

Erythropoietin, ferritin, haptoglobin, hemoglobin and transferrin receptor in metabolic syndrome: a case control study

Several genetic polymorphisms interact with overweight/obesity to influence serum lipid levels

Association between 9p21 genetic variants and mortality risk in a prospective cohort of patients with type 2 diabetes (ZODIAC-15)

Single nucleotide polymorphisms (SNPs) involved in insulin resistance, weight regulation, lipid metabolism and inflammation in relation to metabolic syndrome: an epidemiological study

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page