PEDF decreases cardiomyocyte edema during oxygen‑glucose deprivation and recovery via inhibiting lactate accumulation and expression of AQP1

Myocardial edema is divided into cellular edema and interstitial edema; however, the dynamic change of cardiomyocyte edema has not been described in detail. Pigment epithelium-derived factor (PEDF) is known for its protective effects on ischemic cardiomyocytes; however, the association between PEDF and cardiomyocyte edema remains to be fully elucidated. In the present study, rat neonatal left ventricular cardiomyocytes were isolated and treated with oxygen-glucose deprivation (OGD) and recovery. During OGD and recovery, the cardiomyocytes exhibited significant edema following 30 min of OGD (OGD 30 min) and OGD 30 min with recovery for 6 h. PEDF significantly decreased the lactate content and extracellular acidification rate of the OGD-treated cardiomyocytes, thereby reducing cellular osmotic gradients and preventing the occurrence of cell edema. In addition, the glycolytic agonist, fructose-1, 6-diphosphate, eliminated the effect of PEDF on inhibiting edema in the OGD-treated cardiomyocytes. Furthermore, PEDF reduced the protein and mRNA expression of aquaporin 1 (AQP1), and thus downregulated cardiomyocyte edema during the OGD/recovery period. The addition of AQP1 agonist, arginine vasopressin, inhibited the inhibitory effect of PEDF on cardiomyocyte edema during OGD/recovery. In conclusion, the present study revealed a novel mechanism for the regulation of cardiomyocyte edema by PEDF involving lactate levels and the expression of AQP1 during OGD/recovery. The reduction of lactate content during OGD was associated with a decrease in the protein level of AQP1 during OGD/recovery; therefore, PEDF decreased cardiomyocyte edema and cellular apoptosis, prolonging the viability of the cells.