Arrhythmogenic right ventricular dysplasia (ARVD) is an inherited disorder of cardiomyocyte-to-cardiomyocyte adhesion proteins associated with ventricular arrhythmias and sudden cardiac death. It is a characterized by progressive fibrofatty replacement of right ventricular myocardium. The presence of adipose tissue either with or without fibrous tissue, scattered among cardiomyocytes is the histological hallmark of the disease. Being in the myocardium, adipocytes trigger damage to cardiomyocytes, thus causing electrical instability of the right ventricular myocardium, but the molecular pathogenesis of such an electrical instability in ARVD is still unclear. Since (i) adipose tissue replacement of cardiomyocytes is the most essential histological finding in ARVD, (ii) nerve growth factor (NGF) exerts an arrhythmogenic effect related to sudden cardiac death, and (iii) adipose tissue produces NGF and brain-derived neurotrophic factor (BDNF), the aim of the present study is to analyze immunohistochemically ARVD-related adipocytes with special attention to the expression of NGF and related neurotrophins, BDNF and neurotrophin-3 (NT-3) and their respective TrkA, TrkB and TrkC receptors. Eight cases with ARVD were autopsy proven. The present results demonstrate that the intramyocardial adipocytes and cardiomyocytes in ARVD express NGF/TrkA and NT-3/TrkC, suggesting that they may play a substantial part in life-threatening myocardial electrical instability.
Fontaine G, Guiraudon G, Frank R, Vedel J, Grosgogeat Y, Cabrol C, et al. Stimulation studies and epicardial mapping in ventricular tachycardia: study of mechanisms and selection for surgery. In: Kulbertus HE, editor. Reentrant Arrhythmias: Mechanisms and Treatment. Lancaster: MTP Press Limited; 1977; pp 334-350.
More D, O`Brien K, Shaw J. Arrhythmogenic right ventricular dysplasia in the elderly. Pacing Clin Electrophysiol. 2002; 25: 1266-1269. DOI: 10.1046/j.1460-9592.2002.01266.x
Azaouagh A, Churzidse S, Konorza T, Erbel R. Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a review and update. Clin Res Cardiol. 2011; 100:383-394. DOI: 10.1007/s00392-011-0295-2
Tabib A, Loire R, Chalabreysse L, D. Meyronnet, Miras A, Malicier D, et al. Circumstances of death and gross and microscopic observations in a series of 200 cases of sudden death associated with arrhythmogenic right ventricular cardiomyopathy and/or dysplasia. Circulation 2003; 108: 3000- 3005. DOI: 10.1161/01.CIR.0000108396.65446.21
Matolweni LO, Bardien S, Rebello G, Oppon E, Munclinger M, Ramesar R, et al. Arrhythmogenic right ventricular cardiomyopathy type 6 (ARVC6): support for the locus assignment, narrowing of the critical region and mutation screening of three candidate genes. BMC Med Genet 2006; 7: 29. DOI: 10.1186/1471-2350-7-29
Thiene G, Corrado D, Basso C. Arrhythmogenic right ventricular cardiomyopathy/dysplasia. Orphanet J Rare Dis 2007; 2: 45-61. DOI: 10.1186/1750-1172-2-45.
Awad MM, Calkins H, Judge DP. Mechanisms of disease: molecular genetics of arrhythmogenic right ventricular dysplasia/ cardiomyopathy. Nat Clin Pract Cardiovasc Med 2008; 5: 258-267. DOI: 10.1038/ncpcardio1182
Yang Z, Bowles NE, Scherer SE, Taylor MD, Kearney DL, Ge S, et al. Desmosomal dysfunction due to mutations in desmoplakin causes arrhythmogenic right ventricular dysplasia/ cardiomyopathy. Circ Res 2006; 99: 646-655. DOI: 10.1161/01.RES.0000241482.19382.c6
Fontaine G, Chen H-s V. Arrhythmogenic right ventricular dysplasia back in force. Am J Cardiol 2014; 113: 1735-1739. DOI: 10.1016/j.amjcard.2014.03.001
Calore M, Lorenzon A, De Bortoli M, Poloni G, Rampazzo A. Arrhythmogenic cardiomyopathy: a disease of intercalated discs. Cell Tissue Res 2015; 360:491-500. DOI: 10.1007/ s00441-014-2015-5
Cao JM, Chen LS, KenKnight BH, Ohara T, Lee MH, Tsai J, et al. Nerve sprouting and sudden cardiac death. Circ Res. 2000; 86: 816-821. DOI:10.1161/01.RES.86.7.816
Bloom HL. Beyond beta-blockade: Nerve growth factor and arrhythmia. Heart Rhythm 2007; 4: S437-S448. DOI: 10.1016/j.hrthm.2007.06.017
Sornelli F, Fiore M, Chaldakov GN, Aloe L. Adipose tissuederived nerve growth factor and brain-derived neurotrophic factor: results from experimental stress and diabetes. Gen Physiol Biophys 2009;28:179-183.
Levi-Montalcini R. The nerve growth factor 35 years later. Science 1987; 237: 1154-1162. DOI: 10.1126/sci ence.3306916
Aloe L, Chaldakov GN. The multiple life of nerve growth factor: tribute to Rita Levi-Montalcini (1909-2012). Balkan Med J 2013; 30: 4-7. DOI: 10.5152/balkan medj.2013.003]
Abe T, Morgan DA, Gutterman DD. Protective role of nerve growth factor against postischemic dysfunction of sympathetic coronary innervation. Circulation 1997; 95: 213-220. DOI: 10.1161/01.CIR.95.1.213
Chaldakov GN, Fiore M, Stankulov IS, Manni L, Hristova MG, Antonelli A, et al. Neurotrophin presence in human coronary atherosclerosis and metabolic syndrome: a role for NGF and BDNF in cardiovascular disease? Prog Brain Res 2004; 146: 279-289. DOI: 10.1016/S0079- 6123(03)46018-4
Yanev S, Fiore M, Hinev A, Ghenev PI, Hristova MG, Panayotov P, et al. From antitubulins to trackins. Biomed Rev 2016; 27: 59-67.
Cushing P, Bhalla R, Johnson AM, Rushlow WJ, Meakin SO, Belliveau DJ. Nerve growth factor increases connexin43 phosphorylation and gap junctional intercellular communication. J Neurosci Res 2005; 82:788-801. DOI: 10.1002/jnr.20689
Franzoso M, Zaglia T, Mongillo M. Putting together the clues of the everlasting neuro-cardiac liaison. Biochim Biophys Acta. 2016; 1863(7 Pt B):1904-1915. DOI: 10.1016/j. bbamcr.2016.01.009.
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