Expression of Connexin 43 in the Myocardium in Sudden Unexplained Nocturnal Death Syndrome
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초록
Sudden unexplained nocturnal death syndrome (SUNDS) occurs predominantly in Southeast Asian people including Koreans. SUNDS is problematic for forensic pathologists because the diagnosis depends on the “exclusion of diagnosis.” Moreover, the pathogenesis of SUNDS is still unclear although some cases are known to be intimately related to the Brugada syndrome. Connexin 43 (Cx43) is a principal protein of gap junction in adult cardiac myocytes, being distributed to the intercalated discs and phosphorylated in normal condition. Ischemia and hypoxia alter the expression of total Cx43 (tCx43) resulting in redistribution of non-phosphorylated Cx43 (npCx43) to the sarcoplasm or lateral cell borders of cardiac myocytes by continuing dephosphorylation. This study aimed to compare the immunoexpression pattern of Cx43 in the cardiac myocytes of SUNDS and ischemic heart disease (IHD). The study group was 26 cases of SUNDS and the control group of 24 cases of IHD with severe coronary atherosclerosis, showing no myocardial ischemic change. There was a significantly different expression of both tCx43 and npCX43 between the SUNDS and IHD group. A greater reduction in both tCx43 and npCx43 and a more delayed redistribution pattern was seen in the myocardium of SUNDS when compared with IHD. In conclusion, these results suggest that the reduced Cx43 expression in SUNDS may be inherent and indicate a risk of arrhythmia.
Abstract
Sudden unexplained nocturnal death syndrome (SUNDS) occurs predominantly in Southeast Asian people including Koreans. SUNDS is problematic for forensic pathologists because the diagnosis depends on the “exclusion of diagnosis.” Moreover, the pathogenesis of SUNDS is still unclear although some cases are known to be intimately related to the Brugada syndrome. Connexin 43 (Cx43) is a principal protein of gap junction in adult cardiac myocytes, being distributed to the intercalated discs and phosphorylated in normal condition. Ischemia and hypoxia alter the expression of total Cx43 (tCx43) resulting in redistribution of non-phosphorylated Cx43 (npCx43) to the sarcoplasm or lateral cell borders of cardiac myocytes by continuing dephosphorylation. This study aimed to compare the immunoexpression pattern of Cx43 in the cardiac myocytes of SUNDS and ischemic heart disease (IHD). The study group was 26 cases of SUNDS and the control group of 24 cases of IHD with severe coronary atherosclerosis, showing no myocardial ischemic change. There was a significantly different expression of both tCx43 and npCX43 between the SUNDS and IHD group. A greater reduction in both tCx43 and npCx43 and a more delayed redistribution pattern was seen in the myocardium of SUNDS when compared with IHD. In conclusion, these results suggest that the reduced Cx43 expression in SUNDS may be inherent and indicate a risk of arrhythmia.
참고문헌 (17)
- Cheng J, "Sudden unexplained nocturnal death syndrome in Southern China: an epidemiological survey and SCN5A gene screening", Am J Forensic Med Pathol, 32, pp.359~363 (2011)
- Vatta M, "Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome", Hum Mol Genet, 11, pp.337~345 (2002)
- Liu C, "Is sudden unexplained nocturnal death syndrome in Southern China a cardiac sodium channel dysfunction disorder?", Forensic Sci Int, 236, pp.38~45 (2014)
- Schulz R, "Connexin 43 is an emerging therapeut ic target in i schemia", reper fus ion injury, cardioprotection and neuroprotection, 2015, pp.153, 90~106
- Lampe PD, "The effects of connexin phosphorylation on gap junctional communication", Int J Biochem Cell Biol, 36, pp.1171~1186 (2004)
- Beardslee MA, "Dephosphorylation and intracellular redistribution of ventricular connexin43 during electrical uncoupling induced by ischemia", Circ Res, 87, pp.656~662 (2000)
- Matsushita S, "Alterations of phosphorylation state of connexin 43 during hypoxia and reoxygenation are associated with cardiac function", J Histochem Cytochem, 54, pp.343~353 (2006)
- Kawamoto O, "Immunohistochemistry of connexin43 and zonula occludens-1 in the myocardium as markers of early ischemia in autopsy material", Histol Histopathol, 29, pp.767~775 (2014)
- 안재우, "The Efficacy of Connexin 43 Expression in the Myocardium as an Early Ischemic Marker in Forensic Autopsy", 대한법의학회지, 39(1), pp.6~11 (2015), 대한법의학회
- Michela P, "Role of connexin 43 in cardiovascular diseases", Eur J Pharmacol, 768, pp.71~76 (2015)
- Johansen D, "Ischemia induces closure of gap junctional channels and opening of hemichannels in heart-derived cells and tissue", Cell Physiol Biochem, 28, pp.103~114 (2011)
- Teunissen BE, "Regulation of myocardial connexins during hypertrophic remodelling", Eur Heart J, 25, pp.1979~1989 (2004)
- Chen X, "Myocardial Cx43 expression in the cases of sudden death due to dilated cardiomyopathy", Forensic Sci Int, 162, pp.170~173 (2006)
- Yoshida T, "Relationships between clinical characteristics and decreased plakoglobin and connexin 43 expressions in myocardial biopsies from patients with arrhythmogenic right ventricular cardiomyopathy", Int Heart J, 56, pp.626~631 (2015)
- van Rijen HV, "Slow conduction and enhanced anisotropy increase the propensity for ventricular tachyarrhythmias in adult mice with induced deletion of connexin43", Circulation, 109, pp.1048~1055 (2004)
- Nademanee K, "Fibrosis, connexin-43, and conduction abnormalities in the brugada syndrome", J Am Coll Cardiol, 66, pp.1976~1986 (2015)
- Hatanaka K, "Down-regulation of connexin43 in early myocardial ischemia and protective effect by ischemic preconditioning in rat hearts in vivo", Jpn Heart J, 45, pp.1007~1019 (2004)