Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia.
Ventricular tachyarrhythmias are the main cause of sudden death in patients after myocardial infarction. Here we show that transplantation of embryonic cardiomyocytes (eCMs) in myocardial infarcts protects against the induction of ventricular tachycardia (VT) in mice. Engraftment of eCMs, but not skeletal myoblasts (SMs), bone marrow cells or cardiac myofibroblasts, markedly decreased the incidence of VT induced by in vivo pacing. eCM engraftment results in improved electrical coupling between the surrounding myocardium and the infarct region, and Ca2+ signals from engrafted eCMs expressing a genetically encoded Ca2+ indicator could be entrained during sinoatrial cardiac activation in vivo. eCM grafts also increased conduction velocity and decreased the incidence of conduction block within the infarct. VT protection is critically dependent on expression of the gap-junction protein connexin 43 (Cx43; also known as Gja1): SMs genetically engineered to express Cx43 conferred a similar protection to that of eCMs against induced VT. Thus, engraftment of Cx43-expressing myocytes has the potential to reduce life-threatening post-infarct arrhythmias through the augmentation of intercellular coupling, suggesting autologous strategies for cardiac cell-based therapy.
Institute of Physiology I, Life and Brain Center, University of Bonn, Bonn 53105, Germany.
Wilhelm
W
Roell
Thorsten
T
Lewalter
Philipp
P
Sasse
Yvonne N
YN
Tallini
Bum-Rak
BR
Choi
Martin
M
Breitbach
Robert
R
Doran
Ulrich M
UM
Becher
Seong-Min
SM
Hwang
Toktam
T
Bostani
Julia
J
von Maltzahn
Andreas
A
Hofmann
Shaun
S
Reining
Britta
B
Eiberger
Bethann
B
Gabris
Alexander
A
Pfeifer
Armin
A
Welz
Klaus
K
Willecke
Guy
G
Salama
Jan W
JW
Schrickel
Michael I
MI
Kotlikoff
Bernd K
BK
Fleischmann
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000150:complications* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology; D006321:Heart / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000637:transplantation*; D010477:Perfusion
D018031:Connexin 43