AAV9-αMHC-GFP

Voltage-dependent anion channel 2 (VDAC2) is a mitochondrial outer membrane porin known to play an important role in apoptosis and calcium signaling. To elucidate the role of VDAC2 in calcium homeostasis, researchers generated a ventricular myocyte-specific developmental deletion of Vdac2 in mice. These results show that the loss of VDAC2 in the myocardium leads to a severe impairment of excitation-contraction coupling by altering intracellular and mitochondrial calcium signaling. Researchers also observed adverse cardiac remodeling that progressed to severe cardiomyopathy and death. Reintroduction of VDAC2 in 6-week-old knockout mice partially rescued the cardiomyopathy phenotype. In a mouse model of pressure overload-induced heart failure, activation of VDAC2 by efsevin increased cardiac contractility. Together, these results suggest that VDAC2 plays a critical role in cardiac function by affecting cellular calcium signaling.

Here, researchers evaluated the cardiac ventricular myocyte-specific reintroduction of VDAC2 in KO and WT mice using western blotting and qRT-PCR (Figure 1a, b). Serial echocardiography was performed in these mice until 10 weeks after injection (16-week-old mice) to obtain comparable results. Compared with KO mice injected with the control AAV9-αMHC-GFP vector, KO mice injected with the AAV9-αMHC-VDAC2-GFP vector showed relative improvement in EF, FS, and LV volume, and a decrease in LV diameter, and improved cardiac structure and function were observed (Figure 1c-g). Complete restoration of the phenotype was not observed, however, reintroduction of VDAC2 contributed to improved cardiac function.

Figure 1. Partial rescue of HF phenotype upon VDAC2 reintroduction. (Shankar T S, et al., 2021)