Follistatin-Like 1 Attenuates Ischemia/Reperfusion Injury in Cardiomyocytes via Regulation of Autophagy

The cardioprotective effect of FSTL1 has been extensively studied in recent years, but its role in myocardial ischemia/reperfusion injury (IRI) is unclear. In this study, we investigated the effect of FSTL1 pretreatment on myocardial IRI as well as the possible involvement of autophagic pathways in its effects.

The effects of FSTL1 on the viability and apoptosis of rat cardiomyocytes were investigated after exposure of cardiomyocytes to hypoxia/ischemia by using the CCK-8 assay and Annexin V/PI staining. Further, western blot analysis was used to detect the effects of FSTL1 pretreatment on autophagy-associated proteins, and confocal microscopy was used to observe autophagic flux. To confirm the role of autophagy, the cells were treated with the autophagy promoter rapamycin or the autophagy inhibitor 3-methyladenine, and cell viability and apoptosis during IRI were observed. These effects were also observed after treatment with rapamycin or 3-methyladenine followed by FSTL1 administration and IRI.

FSTL1 pretreatment significantly increased viability and reduced apoptosis in cardiomyocytes exposed to hypoxia/ischemia conditions. Further, FSTL1 pretreatment affected the levels of the autophagy-related proteins and enhanced autophagic flux during IRI. In addition, cell viability was enhanced and apoptosis was decreased by rapamycin treatment, while these effects were reversed by 3-MA treatment. However, when the myocardial cells were pretreated with rapamycin or 3-methyladenine, there was no significant change in their viability or apoptosis with FSTL1 treatment during IRI.

FSTL1 plays a protective role in myocardial IRI by regulating autophagy.