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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

Published online by Cambridge University Press:  17 December 2019

Fábio R. Lodi
Affiliation:
Discipline of Descriptive and Topographic Anatomy, Department of Morphology and Genetics, Federal University of São Paulo, São Paulo, São Paulo, Brazil
Luiz F. Palma*
Affiliation:
Discipline of Descriptive and Topographic Anatomy, Department of Morphology and Genetics, Federal University of São Paulo, São Paulo, São Paulo, Brazil Health School of Faculdades Metropolitanas Unidas – FMU, São Paulo, São Paulo, Brazil
Nathalia C. de Victo
Affiliation:
Health School of Faculdades Metropolitanas Unidas – FMU, São Paulo, São Paulo, Brazil
Luís G. Alonso
Affiliation:
Discipline of Descriptive and Topographic Anatomy, Department of Morphology and Genetics, Federal University of São Paulo, São Paulo, São Paulo, Brazil
Luís O. C. de Moraes
Affiliation:
Discipline of Descriptive and Topographic Anatomy, Department of Morphology and Genetics, Federal University of São Paulo, São Paulo, São Paulo, Brazil
*
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: [email protected]

Abstract

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.

Type
Original Article
Copyright
© Cambridge University Press 2019

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References

Noonan, JA, Nadas, AS.The hypoplastic left heart syndrome: an analysis of 101 cases. Pediatr Clin North Am 1958; 5: 10291056.10.1016/S0031-3955(16)30727-1CrossRefGoogle ScholarPubMed
Reamon-Buettner, SM, Borlak, J.TBX5 mutations in non-Holt–Oram syndrome (HOS) malformed hearts. Hum Mutat 2004; 24: 104111.10.1002/humu.9255CrossRefGoogle ScholarPubMed
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: 13971405.10.1093/hmg/ddn027CrossRefGoogle ScholarPubMed
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.Google Scholar
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]. http://omim.org/entry/121014.Google Scholar
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: 225230.10.1002/ajmg.a.20366CrossRefGoogle Scholar
Wessels, MW, Berger, RM, Frohn-Mulder, IM, et al.Autosomal dominant inheritance of left ventricular outflow tract obstruction. Am J Med Genet 2005; 134: 171179.10.1002/ajmg.a.30601CrossRefGoogle Scholar
Chein, KR.Molecular Basis of Cardiovascular Disease: A Companion to Braunwald’s Heart Disease. 2nd edn. Saunders, Philadelphia, 1999.Google Scholar
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: 173186.10.1016/S0027-5107(01)00160-9CrossRefGoogle Scholar
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: 840852.10.1136/hrt.37.8.840CrossRefGoogle Scholar
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: 558568.10.1016/S0002-8703(97)70151-0CrossRefGoogle ScholarPubMed
Beyer, EC, Paul, DL, Goodenough, DA.Connexin family of gap junction proteins. J Membr Biol 1990; 116: 187194.10.1007/BF01868459CrossRefGoogle ScholarPubMed
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: 886900.10.1016/S0008-6363(96)00131-9CrossRefGoogle Scholar
Lev, M.Pathologic anatomy and interrelationship of hypoplasia of the aortic tract complexes Lab Invest 1952; 1: 6170.Google ScholarPubMed
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: 13231329.10.1056/NEJM199505183322002CrossRefGoogle ScholarPubMed
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.Google ScholarPubMed
Weidmann, S.The diffusion of radiopotassium across intercalated disks of mammalian cardiac muscle. J Physiol 1966; 187: 323342.10.1113/jphysiol.1966.sp008092CrossRefGoogle ScholarPubMed
Severs, NS, Coppen, SR, Dupont, E, Yeh, HI, Ko, YS, Matsushita, T. Gap junction alterations in human cardiac disease. Cardiovas Res 2004; 62: 368377.10.1016/j.cardiores.2003.12.007CrossRefGoogle ScholarPubMed
Strachan, T, Read, T.Human Molecular Genetics 4th edn. Garland Science, New York, 2011.Google Scholar
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: 16.10.1016/S1054-8807(98)00011-8CrossRefGoogle ScholarPubMed
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.Google ScholarPubMed
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: 713725.10.1161/01.CIR.90.2.713CrossRefGoogle ScholarPubMed
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: 483495.10.1002/ar.1092430411CrossRefGoogle ScholarPubMed
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: 248253.10.1136/hrt.44.3.248CrossRefGoogle Scholar
Pozzi, M, Trivedi, DB, Kitchiner, D, Arnold, RA. Tetralogy of Fallot: what operation, at which age. Eur J Cardiothorac Surg 2000; 17: 631636.10.1016/S1010-7940(00)00415-2CrossRefGoogle ScholarPubMed
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: 78078510.1161/01.RES.60.5.780CrossRefGoogle ScholarPubMed
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: 871878.10.1161/01.RES.86.8.871CrossRefGoogle ScholarPubMed