The Optimization in Co-Transfection of SERCA2a And Cx43 Genes for
Myocardial Infarction Complications
As our previous study shown, the therapeutic effect of double genes
(SERCA2a and Cx43) on heart failure after myocardial infarction (MI)
were better than that of single gene (SERCA2a or Cx43) therapy on the
basis of bone marrow stem cells (BMSCs) transplantation. Based on
previous research, the aim of this study was to investigate the optimize
ratio of co-delivery of SERCA2a and Cx43 genes for MI therapy after
biotinylated microbubbles (BMBs) transplantation via ultrasonic-targeted
microbubble destruction (UTMD). Forty rats underwent left anterior
descending (LAD) ligation and BMSCs injection into the infarct and
border zones. Four weeks later, double genes of SERCA2a and Cx43 with
different ratios (1:1, 1:2 and 2:1) were co-delivered into the infarcted
heart via the UTMD. Cardiac mechano-electrical function was determined
at 4-wk after gene delivery, and the hearts of the rats were harvested
for measurement of MI size and detection of SERCA2a and Cx43 expression.
Q-PCR analysis of the expression of Nkx2.5 and GATA4 in the myocardial
infarct zone and measurement of neovascularization in infarcted heart.
After comparing the therapeutic effects of different co-gene ratios, the
SERCA2a/Cx43-1:2 group shown remarkable cardiac electrical stability and
strengthen the role of anti-arrhythmia. In conclusion, the optimum ratio
of SERCA2a/Cx43 gene is 1:2, which take advantageous in maintaining
cardiac electrophysiological stability.