Up-regulation of connexin45 in heart failure.

@article{citeulike:437104, abstract = {INTRODUCTION: Heart failure is associated with reduced expression of the major gap junction protein connexin43 (Cx43), which may contribute to arrhythmias and sudden cardiac death in this patient population. Other cardiac connexins may be altered as well. Because connexin45 (Cx45) has been shown to colocalize with Cx43, we determined whether the number, size, or distribution of Cx45 gap junctions is altered in the failing heart. METHODS AND RESULTS: Cx45 expression levels were measured by immunoblotting and quantitative immunostaining in failing and control human left ventricles. Total Cx45 protein was significantly (P = 0.021) up-regulated 1.8-fold in failing hearts. Cx45 immunohistochemical signal was increased by 80\% (P = 0.005) due to a 3.5-fold increase in the number of gap junctions containing Cx45. Cx45 mRNA was not altered in failing hearts, suggesting reduced degradation of Cx45 protein in the failing heart. Cx43 signal, on the other hand, was reduced by 49\% in failing hearts. Double-label experiments demonstrated colocalization of Cx45 and Cx43 in the same gap junctions. CONCLUSION: Cx45 is markedly enhanced in the failing heart. Up-regulation of Cx45 in conjunction with down-regulation of Cx43 could result in abnormal impulse propagation and generation of ventricular arrhythmias, thereby predisposing patients in heart failure to sudden cardiac death.}, address = {Department of Medicine (Cardiovascular Division), Center for Cardiovascular Research, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. kyamada@im.wustl.edu}, author = {Yamada, K. A. and Rogers, J. G. and Sundset, R. and Steinberg, T. H. and Saffitz, J. E. }, citeulike-article-id = {437104}, issn = {1045-3873}, journal = {J Cardiovasc Electrophysiol}, keywords = {cardiac, connexin, connexin45, cx45, disease, electrophysiology, heart\_failure, myocardium}, month = {November}, number = {11}, pages = {1205--1212}, posted-at = {2005-12-14 18:32:56}, priority = {2}, title = {Up-regulation of connexin45 in heart failure.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/14678136}, volume = {14}, year = {2003} }

TY - JOUR ID - citeulike:437104 L3 - citeulike-article-id:437104 TI - Up-regulation of connexin45 in heart failure. JF - J Cardiovasc Electrophysiol VL - 14 IS - 11 SP - 1205 EP - 1212 AD - Department of Medicine (Cardiovascular Division), Center for Cardiovascular Research, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. kyamada@im.wustl.edu SN - 1045-3873 N2 - INTRODUCTION: Heart failure is associated with reduced expression of the major gap junction protein connexin43 (Cx43), which may contribute to arrhythmias and sudden cardiac death in this patient population. Other cardiac connexins may be altered as well. Because connexin45 (Cx45) has been shown to colocalize with Cx43, we determined whether the number, size, or distribution of Cx45 gap junctions is altered in the failing heart. METHODS AND RESULTS: Cx45 expression levels were measured by immunoblotting and quantitative immunostaining in failing and control human left ventricles. Total Cx45 protein was significantly (P = 0.021) up-regulated 1.8-fold in failing hearts. Cx45 immunohistochemical signal was increased by 80% (P = 0.005) due to a 3.5-fold increase in the number of gap junctions containing Cx45. Cx45 mRNA was not altered in failing hearts, suggesting reduced degradation of Cx45 protein in the failing heart. Cx43 signal, on the other hand, was reduced by 49% in failing hearts. Double-label experiments demonstrated colocalization of Cx45 and Cx43 in the same gap junctions. CONCLUSION: Cx45 is markedly enhanced in the failing heart. Up-regulation of Cx45 in conjunction with down-regulation of Cx43 could result in abnormal impulse propagation and generation of ventricular arrhythmias, thereby predisposing patients in heart failure to sudden cardiac death. KW - cardiac KW - connexin KW - connexin45 KW - cx45 KW - disease KW - electrophysiology KW - heart_failure KW - myocardium AU - Yamada, KA AU - Rogers, JG AU - Sundset, R AU - Steinberg, TH AU - Saffitz, JE PY - 2003/11// UR - http://view.ncbi.nlm.nih.gov/pubmed/14678136 ER -