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10.1016/j.jacc.2016.07.779 http://scihub22266oqcxt.onion/10.1016/j.jacc.2016.07.779 C5373649!5373649!27810048     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\27810048.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       J+Am+Coll+Cardiol 2016 ; 68 (19): 2086-96 Nephropedia Template TP {{tp|p=27810048|t=2016. Patient-specific and genome-edited induced pluripotent stem cell-derived cardiomyocytes elucidate single cell phenotype of Brugada Syndrome |pdf=|usr=}}{{27810048}} gab.com Text Patient-specific and genome-edited induced pluripotent stem cell-derived cardiomyocytes elucidate single cell phenotype of Brugada Syndrome JO: J Am Coll Cardiol http://www.kidney.de/pget.php?&tw=1&pmid=27810048 #FOAvip Background: Brugada Syndrome is a disorder associated with characteristic ECG precordial ST elevation and predisposes afflicted patients to ventricular fibrillation and sudden cardiac death. Despite marked achievements in outlining the organ level pathophysiology of the disorder, the understanding of human cellular phenotype has lagged due to lack of adequate human cellular models of the disorder. Methods and Results: We recruited two patients with Type 1 Brugada Syndrome (BrS) carrying two different SCN5A variants and two healthy controls. We generated induced pluripotent stem cells (iPSCs) from their skin fibroblasts by using integration-free Sendai virus. We utilized directed differentiation to create purified populations of iPSC-derived cardiomyocytes (iPSC-CMs). BrS iPSC-CMs showed reductions in inward Na+ current density and reduced maximal upstroke velocity of action potential compared to healthy control iPSC-CMs. Furthermore, BrS iPSC-CMs showed increased burden of triggered activity, abnormal Ca2+ transients, and beating interval variation. Correction of the causative variant by genome editing was performed and resultant iPSC-CMs showed resolution of triggered activity and abnormal Ca2+ transients. Gene expression profiling of iPSC-CMs showed clustering of BrS compared to controls. Furthermore, BrS iPSC-CM gene expression correlated with gene expression from BrS human cardiac tissue gene expression. Conclusions: Patient-specific iPSC-CMs are able to recapitulate single cell phenotype features of BrS, including blunted inward sodium current, increased triggered activity and abnormal Ca2+ handling. This novel human cellular model creates future opportunities to further elucidate cellular disease mechanism and identify novel therapeutic targets. Twit Text FOAVip Patient-specific and genome-edited induced pluripotent stem cell-derived cardiomyocytes elucidate single cell phenotype of Brugada Syndrome ????J Am Coll Cardiol http://www.kidney.de/pget.php?&tw=1&pmid=27810048 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27810048 #FOAvip English Wikipedia <ref>{{Cite pmid|27810048}}</ref> Patient-specific and genome-edited induced pluripotent stem cell-derived cardiomyocytes elucidate single cell phenotype of Brugada Syndrome #MMPMID27810048 Liang P; Sallam K; Wu H; Li Y; Itzhaki I; Garg P; Zhang Y; Vermglinchan V; Lan F; Gu M; Gong T; Zhuge Y; He C; Ebert AD; Sanchez-Freire V; Churko J; Hu S; Sharma A; Lam CK; Scheinman MM; Bers DM; Wu JC J Am Coll Cardiol 2016[Nov]; 68 (19): 2086-96 PMID27810048show ga Background: Brugada Syndrome is a disorder associated with characteristic ECG precordial ST elevation and predisposes afflicted patients to ventricular fibrillation and sudden cardiac death. Despite marked achievements in outlining the organ level pathophysiology of the disorder, the understanding of human cellular phenotype has lagged due to lack of adequate human cellular models of the disorder. Methods and Results: We recruited two patients with Type 1 Brugada Syndrome (BrS) carrying two different SCN5A variants and two healthy controls. We generated induced pluripotent stem cells (iPSCs) from their skin fibroblasts by using integration-free Sendai virus. We utilized directed differentiation to create purified populations of iPSC-derived cardiomyocytes (iPSC-CMs). BrS iPSC-CMs showed reductions in inward Na+ current density and reduced maximal upstroke velocity of action potential compared to healthy control iPSC-CMs. Furthermore, BrS iPSC-CMs showed increased burden of triggered activity, abnormal Ca2+ transients, and beating interval variation. Correction of the causative variant by genome editing was performed and resultant iPSC-CMs showed resolution of triggered activity and abnormal Ca2+ transients. Gene expression profiling of iPSC-CMs showed clustering of BrS compared to controls. Furthermore, BrS iPSC-CM gene expression correlated with gene expression from BrS human cardiac tissue gene expression. Conclusions: Patient-specific iPSC-CMs are able to recapitulate single cell phenotype features of BrS, including blunted inward sodium current, increased triggered activity and abnormal Ca2+ handling. This novel human cellular model creates future opportunities to further elucidate cellular disease mechanism and identify novel therapeutic targets. äPatient-specific and genome-edited induced pluripotent stem cell-deriv(epmc).pdf DeepDyve Pubget Overpricing