| Autor: |
Fernandes S; INSERM, l'institut du thorax, Nantes, France., van Rijen HV, Forest V, Evain S, Leblond AL, Mérot J, Charpentier F, de Bakker JM, Lemarchand P |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of cellular and molecular medicine [J Cell Mol Med] 2009 Sep; Vol. 13 (9B), pp. 3703-12. Date of Electronic Publication: 2009 Mar 06. |
| DOI: |
10.1111/j.1582-4934.2009.00740.x |
| Abstrakt: |
Cell-based therapies have great potential for the treatment of cardiovascular diseases. Recently, using a transgenic mouse model Roell et al. reported that cardiac engraftment of connexin43 (Cx43)-overexpressing myoblasts in vivo prevents post-infarct arrhythmia, a common cause of death in patients following heart attack. We carried out a similar study but in a clinically relevant context via transplantation of autologous connexin43-overexpressing myoblasts in infarcted rats. Seven days after coronary ligation, rats were randomized into three groups: a control group injected with myoblasts, a null group injected with myoblasts transduced with an empty lentivirus vector (null) and a Cx43 group injected with myoblasts transduced with a lentivirus vector encoding connexin43. In contrast to Roell's report, arrhythmia occurrence was not statistically different between groups (58%, 64% and 48% for the control (n= 12), null (n= 14) and Cx43 (n= 23) groups, respectively, P= 0.92). Using ex vivo intramural monophasic action potential recordings synchronous electrical activity was observed between connexin43-overexpressing myoblasts and host cardiomyocytes, whereas such synchrony did not occur in the null-transduced group. This suggests that ex vivo connexin43 gene transfer and expression in myoblasts improved intercellular electrical coupling between myoblasts and cardiomyocytes. However, in our model such electrical coupling was not sufficient to decrease arrhythmia induction. Therefore, we would suggest a note of caution on the use of combined Cx43 gene and cell therapy to prevent post-infarct arrhythmias in heart failure patients. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
Plný text