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

ABSTRACT: 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.

SUBMITTER: Huang B 

PROVIDER: S-EPMC6445592 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature