Combined treatment with systemic resveratrol and resveratrol preconditioned stem cells maximizes antofibrotic action in diabetic cardiomyopathy.
Resveratrol exerts multi-potential therapeutics on diabetic cardiac dysfunctions. On cardiac cellular levels, it promotes stem cell prolifesration, better differentiation and survival. Wnt/β-catenin signaling pathway plays crucial role in DCM, thus we aimed at investigating the effect of one therapeutic approach with RSV and combined treatment of RSV with MSCs that was either RSV-preconditioned or not on Wnt/β-catenin signaling pathway of STZ-induced DCM. The rats were divided into control (c), diabetic (DM), diabetic treated with systemic RSV (DM-RSV), diabetic treated with RSV and non-conditioned MSCs (DM-RSV-MSCs) and diabetic treated with RSV given systemic and incubated with MSCs (DM-RSV-MSCc). Echo-cardiography showed significant improvement of EF% and FF% in all groups treated with RSV with significant increase observed in in DM-RSV-MSCc compared to DM-RSV-MSCs that was associated with attenuation of cardiac fibrosis together with decreased area % for cardiac levels of sFRP2 and Wnt/β-catenin. In conclusion, combined use of RSV (systemically and in culture media of MSCs) significantly improved diabetic cardiac remodeling and fibrosis via attenuation of sFRP2 and the downstream Wnt/β-catenin pathway.