Dataset for: Tadalafil, a long acting phosphodiesterase inhibitor, promotes bone marrow stem cell survival and their homing into ischemic myocardium for cardiac repair

The aim was to evaluate the tadalafil-mediated effects at molecular level on bone marrow-derived mesenchymal stem cells (MSCs) survival and their homing into the infarcted hearts to promote cardiac repair and improve function. MSCs were pretreated in vitro with tadalafil (+/-H2O2, oxidative stress) and with PKG, MAPK, FasL, nitric oxide synthase (NOS) (L-NAME), CXCR4 (AMD3100), or miR-21 inhibitors (+/-luciferase construction +/-Fas) for 2h before tadalafil. Rats were subjected to acute myocardial infarction (AMI), and then followed by injection of saline or 1.5x106 MSCs-treated +/- tadalafil into infarcted area. In another group, AMI was performed in 1-month post-myelo-ablated rats, were injected intraperitoneally (IP) with tadalafil +/- AMD3100 or L-NAME for 5 days. Also, in another group, AMI mice were treated with IP +/- tadalafil before intravenous injection with 111In-oxine-MSCs followed by CT/SPECT imaging to locate mobilized MSCs. Cardiac function was assessed by echocardiography. MSCs and heart extracts were analyzed by molecular bioassays. Tadalafil-treated MSCs had higher expression of cGMP, NOS, SDF-1α, p-VASP, p-Erk1/2, p-STAT3, p-Akt, PKG1 and Bcl-xl; expression of these molecules was reduced with PKG1, MAPK, NOS or FasL inhibitors. Tadalafil inhibited apoptosis through increased miR-21 expression and improved cell survival by inhibiting Fas (restored by PKG1, MAPK or miR-21 inhibitors). In vivo, heart function, grafted cell survival, MSCs mobilization and homing were improved in tadalafil-treated AMI animals versus controls. Conclusions: Tadalafil prolonged MSCs survival via up-regulation of miR-21 dependent suppression of Fas, and increased MSCs mobilization and their homing into infarcted myocardium resulting in improved cardiac repair and function.