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Horm Metab Res 2009; 41(12): 855-860
DOI: 10.1055/s-0029-1231081
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Epicardial Adipose Tissue and Intracoronary Adrenomedullin Levels in Coronary Artery Disease

G. Iacobellis1 , C. R. di Gioia2 , M. Di Vito2 , L. Petramala3 , D. Cotesta3 , V. De Santis4 , D. Vitale4 , L. Tritapepe4 , C. Letizia3
  • 1Department of Medicine, McMaster University, Hamilton, ON, Canada
  • 2Department of Experimental Medicine, Sapienza University, Rome, Italy
  • 3Department of Clinical Sciences, Sapienza University, Rome, Italy
  • 4Department of Anesthesiology and Intensive Care, Sapienza University, Rome, Italy
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Publication History

received 18.03.2009

accepted 15.06.2009

Publication Date:
21 July 2009 (online)

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Abstract

The aim of the study was to test 1) whether chronic and stable coronary artery disease (CAD) could downregulate epicardial fat adrenomedullin synthesis and secretion, and decrease intracoronary plasma adrenomedullin levels, and 2) whether intracoronary plasma adrenomedullin levels could be related to epicardial adipose tissue adrenomedullin gene and protein expression in subjects with CAD. We examined 12 patients with CAD who required coronary artery bypass graft (CABG) and 10 patients with non-CAD who underwent cardiac surgery for valve replacement. Plasma levels of adrenomedullin were measured in peripheral vein circulation, in left coronary artery (LCA) and coronary sinus (CS) during coronary angiography. Epicardial adipose tissue biopsy for Reverse Transcription and Real-Time PCR (RT-PCR) adrenomedullin mRNA analysis and Western Blotting (WB) protein expression was performed during cardiac surgery in all subjects. Peripheral, LCA, and CS plasma adrenomedullin levels were significantly lower in CAD patients than in those with non-CAD (3.0±0.9 vs. 4.4±0.9 pg/ml p<0.01; 2.9±1 vs. 4.05±0.8 pg/ml, p<0.01, 3.1±0.9 vs. 3.98±0.9 pg/ml p=0.04, respectively). However, CS adrenomedullin levels were not statistically different than those in LCA suggesting that adrenomedullin was not secreted from epicardial fat into the coronary artery lumen. Epicardial fat adrenomedullin mRNA levels and protein expression were lower in patients with CAD than in those with non-CAD (p<0.01 for both). We conclude that 1) epicardial fat adrenomedullin gene and protein expression can be downregulated in CAD subjects, and 2) intracoronary adrenomedullin levels are lower in CAD. No evidence that epicardial adipose tissue really contributes intracoronary adrenomedullin can be provided at this time.

Key words

epicardial adipose tissue - epicardial fat - adrenomedullin - coronary artery disease

References

  • 1 Iacobellis G, Corradi D, Sharma AM. Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart.  Nat Clin Pract Cardiovasc Med. 2005;  2 536-543
    Google Scholar
  • 2 Iacobellis G, Barbaro G. The Double Role of Epicardial Adipose Tissue as Pro- and Anti-inflammatory Organ.  Horm Metab Res. 2008;  40 442-445
    Google Scholar
  • 3 Iacobellis G, Pond CM, Sharma AM. Adiposity of the heart.  Ann Intern Med. 2006;  145 554-555
    Google Scholar
  • 4 Iacobellis G, Gao YJ, Sharma AM. Do cardiac and perivascular adipose tissue play a role in atherosclerosis?.  Curr Diab Rep. 2008;  8 20-24
    Google Scholar
  • 5 Sacks HS, Fain JN. Human epicardial adipose tissue: a review.  Am Heart J. 2007;  153 907-917
    Google Scholar
  • 6 Iacobellis G, Willens HJ, Barbaro G, Sharma AM. Threshold Values of High-risk Echocardiographic Epicardial Fat Thickness.  Obesity (Silver Spring). 2008;  16 887-892
    Google Scholar
  • 7 Iacobellis G, Pellicelli AM, Sharma AM, Grisorio B, Barbarini G, Barbaro G. Relation of Subepicardial Adipose Tissue to Carotid Intima-Media Thickness in Patients With Human Immunodeficiency Virus.  Am J Cardiol. 2007;  99 1470-1472
    Google Scholar
  • 8 Djaberi R, Schuijf JD, van Werkhoven JM, Nucifora G, Jukema JW, Bax JJ. Relation of epicardial adipose tissue to coronary atherosclerosis.  Am J Cardiol. 2008;  102 1602-1607
    Google Scholar
  • 9 Ahn SG, Lim HS, Joe DY, Kang SJ, Choi BJ, Choi SY. Relationship of Epicardial Adipose Tissue by Echocardiography to Coronary Artery Disease.  Heart. 2008;  94 e7
    Google Scholar
  • 10 Jeong JW, Jeong MH, Yun KH, Oh SK, Park EM, Kim YK. Echocardiographic epicardial fat thickness and coronary artery disease.  Circ J. 2007;  71 536-539
    Google Scholar
  • 11 de Vos AM, Prokop M, Roos CJ, Meijs MF, van der Schouw YT, Rutten AL. Peri-coronary epicardial adipose tissue is related to cardiovascular risk factors and coronary artery calcification in post-menopausal women.  Eur Heart J. 2007;  29 777-783
    Google Scholar
  • 12 Iacobellis G, Pistilli D, Gucciardo M, Leonetti F, Miraldi F, Brancaccio G, Leonetti F, Di Mario U, Gallo P, di Gioia CR. Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease.  Cytokine. 2005;  29 251-255
    Google Scholar
  • 13 Iacobellis G, di Gioia CR, Cotesta D, Petramala L, Travaglini C, De Santis V, Vitale D, Tritapepe L, Letizia C. Epicardial adipose tissue adiponectin expression is related to intracoronary adiponectin levels.  Horm Metab Res. 2009;  41 227-231
    Google Scholar
  • 14 Silaghi A, Achard V, Paulmyer-Lacroix O, Scridon T, Tassistro V, Duncea I. Expression of adrenomedullin in human epicardial adipose tissue: role of coronary status.  Am J Physiol Endocrinol Metab. 2007;  293 E1443-E450
    Google Scholar
  • 15 Cheung BM, Li CY, Wong LY. Adrenomedullin: Its Role in the Cardiovascular System.  Sem Vasc Med. 2004;  4 129-134
    Google Scholar
  • 16 Yasu T, Nishikimi T, Kobayashi N, Ikeda N, Ueba H, Nakamura T, Funayama H, Kubo N, Kawakami M, Matsuoka H, Kangawa K, Saito M. Up-regulated synthesis of mature-type adrenomedullin in coronary circulation immediately after reperfusion in patients with anterior acute myocardial infarction.  Regul Pept. 2005;  129 161-166
    Google Scholar
  • 17 Kobayashi K, Kitamura K, Hirayama N. Increased plasma adrenomedullin in acute myocardial infarction.  Am Heart J. 1996;  131 676-680
    Google Scholar
  • 18 Hamid SA, Baxter GF. A critical cytoprotective role of endogenous adrenomedullin in acute myocardial infarction.  J Mol Cell Cardiol. 2006;  41 360-363
    Google Scholar
  • 19 Hojo Y, Uichi I, Katsuki T, Shimada K, Baxter GF. Decreased adrenomedullin production in the coronary circulation of patients with coronary artery disease.  Heart. 2000;  84 88
    Google Scholar
  • 20 Letizia C, De Toma G, Caliumi C, Cerci S, Massa R, Di Iorio R, Alo P, Marinoni E, Diacinti D, D’Erasmo E. Plasma Adrenomedullin Concentrations in Patients with Adrenal Pheochromocytoma.  Horm Metab Res. 2001;  33 290-294
    Google Scholar
  • 21 Etoh T, Doi H, Hanada Y, Kato J, Imamura T, Kitamura K, Koiwaya Y, Eto T. Cardiac secretion of adrenomedullin by percutaneous transluminal coronary angioplasty.  Horm Metab Res. 1997;  29 530-531
    Google Scholar
  • 22 Iacobellis G, Cotesta D, Petramala L, De Santis V, Vitale D, Tritapepe L, Letizia C. Intracoronary adiponectin levels rapidly and significantly increase after coronary revascularization.  Int J Cardiol. 2009 Jan 26;  26 , [Epub ahead of print]
    Google Scholar
  • 23 Ishikawa T, Hatakeyama K, Imamura T, Ito K, Hara S, Date H, Shibata Y, Hikichi Y, Asada Y, Eto T. Increased adrenomedullin immunoreactivity and mRNA expression in coronary plaques obtained from patients with unstable angina.  Heart. 2004;  90 1206-1210
    Google Scholar

Correspondence

Prof. G. IacobellisMD, PhD 

Department of Medicine

St. Joseph's Hospital

50 Charlton Avenue East

Fontbonne Bldg

Hamilton

Ontario L8N 4A6

Canada

Phone: +1/905/521 1155 32739

Fax: +1/905/521 6068

Email: gianluca@ccc.mcmaster.ca

Email: gianluca.iaco@tin.it

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