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Expression of connexin-43 in the cardiac muscle of children diagnosed with hypoplastic left heart syndrome: a Western blot and confocal laser scanning microscopy study

  • Fábio R. Lodi (a1), Luiz F. Palma (a1) (a2), Nathalia C. de Victo (a2), Luís G. Alonso (a1) and Luís O. C. de Moraes (a1)...


Hypoplastic left heart syndrome consists of several structural abnormalities in the left side of the heart and may be associated with a hereditary genetic cause, possibly related to the connexin gene GJA1; however, only a few studies have investigated it. The present study aimed to analyse the expression of connexin-43 in the cardiac muscle of hypoplastic left heart syndrome children by Western blot method and confocal laser scanning microscopy. For that, tissue samples were taken during corrective surgery to treat heart defects. Patients of control group (8) presented any type of heart defect not related to hypoplastic left heart syndrome, connexin-43, or its gene and those of hypoplastic left heart syndrome group (9) presented this disease singly, without any other associated congenital diseases. By means of confocal laser scanning microscopy, it was noticed no connexin-43 qualitative differences in positioning and location pattern between both groups. From Western blot analysis, the connexin-43 expression did not show a statistically significant difference (p = 0.0571) as well. Within the limits of this study, it is suggested that cardiomyocytes of hypoplastic left heart syndrome children are similar in connexin-43 location, distribution, and structural and conformational patterns to those of children with heart defects not related to this protein and its genes.


Corresponding author

Author for correspondence: L. F. Palma, Discipline of Descriptive and Topographic Anatomy, Department of Morphology and Genetics, Federal University of São Paulo, Rua Botucatu, 740 – 04023-900 – São Paulo, São Paulo, Brazil. Tel: +5511991008038; Fax: +551155717597; E-mail:


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1.Noonan, JA, Nadas, AS.The hypoplastic left heart syndrome: an analysis of 101 cases. Pediatr Clin North Am 1958; 5: 10291056.
2.Reamon-Buettner, SM, Borlak, J.TBX5 mutations in non-Holt–Oram syndrome (HOS) malformed hearts. Hum Mutat 2004; 24: 104111.
3.Reamon-Buettner, SM, Ciribilli, Y, Inga, A, Borlak, J. Aloss-of-function mutation in the binding domain of HAND1 predicts hypoplasia of the human hearts. Hum Mol Genet 2008; 17: 13971405.
4.Visoná, SD, Benati, D, Monti, MC, et al.Diagnosis of sudden cardiac death due to early myocardical ischemia: an ultrastructural and immunohistochemical study. Eur J Histochem 2018; 62: 1321.
5.OMIM from National Library of Medicine: data banks [database on the Internet]. Bethsda (MD): National Library of Medicine (US); c1993 [update 2017 Oct 20; cited 2018 Jan 20].
6.Loffredo, CA, Chokkalingam, A, Sill, AM, et al.Prevalence of congenital cardiovascular malformations among relatives of infants with hypoplastic left heart, coarctation of the aorta, and d-transposition of the great arteries. Am J Med Genet 2004; 124: 225230.
7.Wessels, MW, Berger, RM, Frohn-Mulder, IM, et al.Autosomal dominant inheritance of left ventricular outflow tract obstruction. Am J Med Genet 2005; 134: 171179.
8.Chein, KR.Molecular Basis of Cardiovascular Disease: A Companion to Braunwald’s Heart Disease. 2nd edn. Saunders, Philadelphia, 1999.
9.Dasgupta, C, Martinez, AM, Zuppan, CW, Shah, MM, Bailey, LL, Fletcher, WH. Identification of connexin43 gap junction gene mutations in patients with hypoplastic left heart syndrome by denaturing gradient gel electrophoresis (DGGE). Mut Res 2001; 479: 173186.
10.Rose, V, Izukawa, T, Moës, CAF.Syndromes of asplenia and polysplenia: a review of cardiac and non-cardiac malformations in sixty cases with special reference to diagnosis and prognosis. Br Heart J 1975; 37: 840852.
11.Van Praagh, S, Geva, T, Friedberg, DZ, et al.Aortic outflow obstruction in visceral heterotaxy: a study based on twenty postmortem cases. Am Heart J 1997; 133: 558568.
12.Beyer, EC, Paul, DL, Goodenough, DA.Connexin family of gap junction proteins. J Membr Biol 1990; 116: 187194.
13.Van Kempen, M, Vermeulen, J, Moorman, A, Gros, D, Paul, DL, Lamers, WH. Developmental changes of connexin 40 and connexin 43 mRNA. Cardiovasc Res 1996; 32: 886900.
14.Lev, M.Pathologic anatomy and interrelationship of hypoplasia of the aortic tract complexes Lab Invest 1952; 1: 6170.
15.Britz-Cunningham, SH, Shah, M, Zuppan, CW, Fletcher, WH. Mutations of the connexin43 GAP junction gene in patients with heart malformations and defects of laterality. N Engl J Med 1995; 332: 13231329.
16.Sun, LP, Wang, L, Wang, H, Zhang, YH, Pu, JL. Connexin 43 remodeling induced by LMNA gene mutation Glu82Lys in familial dilated cardiomyopathy with atrial ventricular block. Chin Med J 2010; 123: 10581062.
17.Weidmann, S.The diffusion of radiopotassium across intercalated disks of mammalian cardiac muscle. J Physiol 1966; 187: 323342.
18.Severs, NS, Coppen, SR, Dupont, E, Yeh, HI, Ko, YS, Matsushita, T. Gap junction alterations in human cardiac disease. Cardiovas Res 2004; 62: 368377.
19.Strachan, T, Read, T.Human Molecular Genetics 4th edn. Garland Science, New York, 2011.
20.Goldfine, SM, Walcott, B, Brink, PR, Magid, NM, Borer, JS. Myocardial connexin43 expression in left ventricular hypertrophy resulting from aortic regurgitation. Cardiovasc Pathol 1999; 8: 16.
21.Kolcz, J, Drukala, J, Bzowska, M, Rajwa, B, Korohoda, W, Malec, E. The expression of connexin 43 in children with tetralogy of Fallot. Cel Mol Biol Lett 2005; 10: 287303.
22.Peters, NS, Severs, NJ, Rothery, S, Lincoln, C, Yacoub, MH, Green, CR. Spatiotemporal relation between gap junctions and fascia adherens during postnatal development of human ventricular myocardium. Circulation 1994; 90: 713725.
23.Sanchez-Quintana, D, Garcia-Martinez, V, Climent, V, Hurle, JM. Morphological changes in the normal pattern of ventricular myoarchitecture in the developing human heart. Anat Rec 1995; 243: 483495.
24.Deanfield, JE, McKenna, WJ, Hallidie-Smith, KA. Detection of late arrhythmia and conduction disturbances after correction of tetrallogy of Fallot. Br Heart J 1980; 44: 248253.
25.Pozzi, M, Trivedi, DB, Kitchiner, D, Arnold, RA. Tetralogy of Fallot: what operation, at which age. Eur J Cardiothorac Surg 2000; 17: 631636.
26.Delmar, M, Michaels, DC, Johnson, T, Jalife, J. Effects of increasing intercellular resistance on transverse and longitudinal propagation in sheep epicardial muscle. Circ Res 1987; 60: 780785
27.Uzzaman, M, Honjo, H, Takagishi, Y, et al.Remodeling of gap junction coupling in hypertrophied right ventricles of rats with monocrotaline-induced pulmonary hypertension. Circ Res 2000; 86: 871878.


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Expression of connexin-43 in the cardiac muscle of children diagnosed with hypoplastic left heart syndrome: a Western blot and confocal laser scanning microscopy study

  • Fábio R. Lodi (a1), Luiz F. Palma (a1) (a2), Nathalia C. de Victo (a2), Luís G. Alonso (a1) and Luís O. C. de Moraes (a1)...


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