Horm Metab Res 2007; 39(9): 672-676
DOI: 10.1055/s-2007-985823
Original

© Georg Thieme Verlag KG Stuttgart · New York

Apoptosis in Patients with Dilated Cardiomyopathy and Diabetes: A Feature of Diabetic Cardiomyopathy?

F. Kuethe 1 , 2 , H. H. Sigusch 3 , S. R. Bornstein 2 , K. Hilbig 1 , V. Kamvissi 2 , H. R. Figulla 1
  • 1Klinik für Innere Medizin I, Friedrich-Schiller-Universität Jena, Jena, Germany
  • 2Medizinische Klinik III, Universitätsklinikum Carl-Gustav-Carus Dresden, Dresden, Germany
  • 3Klinik für Innere Medizin I, Heinrich-Braun Krankenhaus Zwickau, Zwickau, Germany
Further Information

Publication History

received 05.11.2006

accepted 15.05.2007

Publication Date:
10 September 2007 (online)

Abstract

Background: Dilated cardiomyopathy (DCM) has been suggested to be a consequence of a prior viral infection leading to a chronic inflammatory and immunological reaction that leads to a structural and functional deterioration of the heart. Nevertheless, the results of present studies are conflicting, regarding the natural course of heart diseases associated with detection of viral genome and inflammation. On the other hand, diabetes mellitus (DM) is the leading endocrine disorder worldwide and sufficient to induce a cardiomyopathy. It is not known whether DM contributes to the clinical picture of cardiomyopathy associated with the presence of viral genome or inflammatory cells in the myocardium. Therefore, the present study was undertaken to compare histological, immunohistochemical, biochemical, and functional data as well as the outcome of patients presenting with DCM and positive for DM with patients negative for DM to evaluate for a diabetic contribution in the course of the disease.

Methods: A total of 216 patients were biopsied between January 1998 and April 2003. From 197 patients diagnosed as having DCM, we were able to complete data set regarding the presence of DM in 108 patients, 20 patients with and 88 patients without DM.

Results: There was no significant difference regarding age, gender, body mass index, presence of viral genome and inflammatory cells in the myocardium, left ventricular function and diameter, and the degree of heart insufficiency. There was a significant difference of apoptotic cells in the myocardium of patients with DCM and DM compared to patients with DCM alone (1.7±1.9 vs. 0.2±0.4, p=0.028). During the follow-up of 16 months, left ventricular function improved in both groups significantly, but not between the groups. Death or transplantation-free survival was not significantly different.

Conclusion: The different findings regarding the presence of apoptotic cells suggest a contribution of pathobiological pathways in the patients with DM to the underlying heart disease.

References

  • 1 Richardson P, MacKenna W, Bristow M. et al . Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies.  Circulation. 1996;  93 ((5)) 841-842
  • 2 Kandolf R, Sauter M, Aepinus C. et al . Mechanisms and consequences of enterovirus persistence in cardiac myocytes and cells of the immune system.  Virus Res. 1999;  62 ((2)) 149-158
  • 3 Limas CJ. Autoimmunity in dilated cardiomyopathy and the major histocompatibility complex.  Int J Cardiol. 1996;  54 ((2)) 113-116
  • 4 Kuhl U, Pauschinger M, Noutsias M. et al . High prevalence of viral genomes and multiple viral infections in the myocardium of adults with “idiopathic” left ventricular dysfunction.  Circulation. 2005;  111 ((7)) 887-893 , Epub 2005 Feb 2007
  • 5 Strauer BE, Kandolf R, Mall G. et al . Update 2001 Myocarditis - cardiomyopathy.  Med Klin. 2001;  96 ((10)) 608-625
  • 6 Kuethe F, Sigusch HH, Hilbig K. et al . Detection of viral genome in the myocardium: lack of prognostic and functional relevance in patients with acute dilated cardiomyopathy.  Am Heart J May. 2007;  153 ((5)) 850-858
  • 7 Farhangkhoee H, Khan ZA, Kaur H. et al . Vascular endothelial dysfunction in diabetic cardiomyopathy: pathogenesis and potential treatment targets.  Pharmacol Ther Aug. 2006;  111 ((2)) 384-399
  • 8 Zell R, Klingel K, Bültmann M. et al . Detection of enteroviral RNA from formalin-fixed paraffin-embedded myocardial specimens by nested RT-PCR.  Path Res Pract. 1995;  191 196-199
  • 9 Gow J, Cash P, Behan W. et al . Detection of picornavirus genomic and template RNA strands by a novel semi-nested polymerase chain reaction-technique and agarose-gel electrophoresis.  Electrophoresis Mar. 1995;  16 ((3)) 338-340
  • 10 Lotze U, Egerer R, Tresselt C. et al . Frequent detection of parvovirus B19 genome in the myocardium of adult patients with idiopathic dilated cardiomyopathy.  Med Microbiol Immunol (Berl). 2004;  193 ((2-3)) 75-82 , Epub 2003 Dec 2020
  • 11 Pauschinger M, Bowles NE, Fuentes-Garcia FJ. et al . Detection of adenoviral genome in the myocardium of adult patients with idiopathic left ventricular dysfunction.  Circulation. 1999;  99 ((10)) 1348-1354
  • 12 Aschoff A, Jantz M, Jirikowski GF. In-situ end labelling with bromodeoxyuridine - an advanced technique for the visualization of apoptotic cells in histological specimens.  Horm Metab Res. 1996;  28 ((7)) 311-314
  • 13 Figulla HR, Stille-Siegener M, Mall G. et al . Myocardial enterovirus infection with left ventricular dysfunction: a benign disease compared with idiopathic dilated cardiomyopathy.  J Am Coll Cardiol. 1995;  25 ((5)) 1170-1175
  • 14 Why HJ, Meany BT, Richardson PJ. et al . Clinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis or dilated cardiomyopathy.  Circulation. 1994;  89 ((6)) 2582-2589
  • 15 Badorff C, Lee GH, Lamphear BJ. et al . Enteroviral protease 2A cleaves dystrophin: evidence of cytoskeletal disruption in an acquired cardiomyopathy.  Nat Med. 1999;  5 ((3)) 320-326
  • 16 Brownlee M. Biochemistry and molecular cell biology of diabetic complications.  Nature. 2001;  414 ((6865)) 813-820
  • 17 Lee AY, Chung SS. Contributions of polyol pathway to oxidative stress in diabetic cataract.  Faseb J. 1999;  13 ((1)) 23-30
  • 18 Cooper ME. Importance of advanced glycation end products in diabetes-associated cardiovascular and renal disease.  Am J Hypertens. 2004;  17 ((12 Pt 2)) 31S-38S
  • 19 Hammes HP, Martin S, Federlin K. et al . Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy.  Proc Natl Acad Sci USA. 1991;  88 ((24)) 11555-11558
  • 20 Candido R, Forbes JM, Thomas MC. et al . A breaker of advanced glycation end products attenuates diabetes-induced myocardial structural changes.  Circ Res. 2003;  92 ((7)) 785-792
  • 21 Way KJ, Isshiki K, Suzuma K. et al . Expression of connective tissue growth factor is increased in injured myocardium associated with protein kinase C beta2 activation and diabetes.  Diabetes Sep. 2002;  51 ((9)) 2709-2718
  • 22 Way KJ, Katai N, King GL. Protein kinase C and the development of diabetic vascular complications.  Diabet Med. 2001;  18 ((12)) 945-959
  • 23 Wakasaki H, Koya D, Schoen FJ. et al . Targeted overexpression of protein kinase C beta2 isoform in myocardium causes cardiomyopathy.  Proc Natl Acad Sci USA. 1997;  94 ((17)) 9320-9325
  • 24 Cai L, Kang YJ. Oxidative stress and diabetic cardiomyopathy: a brief review.  Cardiovasc Toxicol. 2001;  1 ((3)) 181-193
  • 25 Fiordaliso F, Leri A, Cesselli D. et al . Hyperglycemia activates p53 and p53-regulated genes leading to myocyte cell death.  Diabetes. 2001;  50 ((10)) 2363-2375
  • 26 Cai L, Wang Y, Zhou G. et al . Attenuation by metallothionein of early cardiac cell death via suppression of mitochondrial oxidative stress results in a prevention of diabetic cardiomyopathy.  J Am Coll Cardiol. 2006;  48 ((8)) 1688-1697
  • 27 Yoon YS, Uchida S, Masuo O. et al . Progressive attenuation of myocardial vascular endothelial growth factor expression is a seminal event in diabetic cardiomyopathy: restoration of microvascular homeostasis and recovery of cardiac function in diabetic cardiomyopathy after replenishment of local vascular endothelial growth factor.  Circulation. 2005;  111 ((16)) 2073-2085
  • 28 Fein FS, Sonnenblick EH. Diabetic cardiomyopathy.  Cardiovasc Drugs Ther Feb. 1994;  8 ((1)) 65-73
  • 29 Ren J, Bode AM. Altered cardiac excitation-contraction coupling in ventricular myocytes from spontaneously diabetic BB rats.  Am J Physiol Heart Circ Physiol. 2000;  279 ((1)) H238-H244
  • 30 Spector KS. Diabetic cardiomyopathy.  Clin Cardiol. 1998;  21 ((12)) 885-887
  • 31 Schannwell CM, Schneppenheim M, Perings S. et al . Left ventricular diastolic dysfunction as an early manifestation of diabetic cardiomyopathy.  Cardiology. 2002;  98 ((1-2)) 33-39

Correspondence

Dr. F. Kuethe

Medizinische Klinik III

Universitätsklinikum Carl Gustav Carus Dresden

Fetscherstrasse 74

01307 Dresden

Germany

Phone: +49/351/458 45 06

Fax: +49/351/458 58 63

Email: Friedhelm.Kuethe@uniklinikum-dresden.de

    >