Abstract 3887: Wnt11 Overexpression in MSCs Protects Myocardium Against Ischemic Reperfusion Injury via Upregulation of GATA-4
We have studied the augmented effect of Wnt11 transfected mesenchymal stem cells (MSCsWnt11) which show upregulation of GATA-4 on cardioprotection. We hyothesize that GATA-4 overexpression mediates cardioprotection. Cardioprotection by MSCs was investigated by 1) co-culture CM with MSCs and 2) transplantation of MSCs (1.5×106 /50μl) into the border area of ischemic rat hearts after ligation of the left anterior descending coronary artery. GATA-4 was overexpressed by transfection of GATA-4 gene via adenoviral vectors to MSCs (MSCsGATA-4). Loss of GATA-4 in MSCsWnt11 was carried out by transfecting GATA-4-siRNA into MSCsWnt11 using oligofectamine. Expression of GATA-4 in MSCsWnt11 was assayed by quantitative PCR. GATA-4 was significantly upregulated in MSCsWnt11 compared to MSCsGFP, especially, when cells were exposed to low oxygen microenvironment (Fig. 1⇓). Hearts transplanted with MSCsWnt11 showed a significant improvement in cardiac function compared to those transplanted with MSCsGFP. TUNEL positive cells in hearts treated with MSCsWnt11 were significantly reduced (0.57±0.17%) compared to MSCsGFP (1.84±0.38% VS 6.51±1.00%, p<0.05). Moreover, annexin-V+ CM were significantly less when co-cultured with MSCsWnt11 and MSCsGATA-4 than those co-cultured with MSCsGFP (Fig. 2⇓). The effect of MSCsWnt11 was abolished by GATA-4-siRNA-MSCsWnt11 (Tab. 1). These results suggest that MSCsWnt11 exert a powerful cardioprotective effect via overexpression of GATA-4.