Prostaglandin E2 reduces swine myocardial ischemia reperfusion injury via increased endothelial nitric oxide synthase and vascular endothelial growth factor expression levels

Abstract

Prostaglandin E2 (PGE2) has been demonstrated to attenuate cardiac ischemia-reperfusion (I/R) injury. However, the underlying mechanism of PGE2 in cardiac I/R injury remains unknown. Upregulated expression levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) were reported in acute myocardial infarction (AMI), and were demonstrated to diminish I/R injury. In the current study the involvement of VEGF and eNOS in the myocardial protective effect of PGE2 were investigated in a catheter-based porcine model of AMI. Twenty-two Chinese miniature pigs were randomized into sham-surgery (n=6), control (n=8) and PGE2 (n=8) groups. PGE2 (1 µg/kg) was injected from 10 min prior to left anterior descending occlusion up to 1 h after reperfusion in the PGE2 group. Subsequently, the hemodynamic parameters were evaluated. Thioflavin-S and Evans Blue double staining were performed to evaluate the extent of the myocardial reperfusion area (RA) and no-reflow area (NRA). Immunohistochemical and western blot analysis were used to evaluate protein expression levels of VEGF and eNOS. Left ventricular (LV) systolic pressure significantly improved and LV end-diastolic pressure significantly decreased in the PGE2 group when compared with the control group 2 h after occlusion and 3 h after reperfusion (P<0.05, respectively). The RA and NRA were smaller in the PGE2 group than in the control group (P<0.05, respectively). Furthermore, PGE2 treatment increased the myocardial content of VEGF and eNOS when compared with the control group (P<0.05, respectively). Thus, the results of the present study demonstrate the cardio-protective mechanisms of PGE2, which may protect the heart from I/R injury via enhancement of VEGF and eNOS expression levels.

Immune Function of Endothelial Cells: Evolutionary Aspects, Molecular Biology and Role in Atherogenesis

“…In doing so, acting through EP4, prostaglandin E2 protects the heart from ischemia–reperfusion injury [ 212 ]. In addition, it reduces swine myocardial ischemia–reperfusion injury by increasing the expression levels of eNOS and VEGF [ 213 ]. EP2 is involved in the repair of postischemic cardiac damage by modulating macrophage recruitment [ 214 ].…”

Targeting Obesity and Diabetes to Treat Heart Failure with Preserved Ejection Fraction

“…ProANP 31–67 also has vasodilatory actions and induces diuresis via inhibition of the basolateral Na + –K + ATPase of the inner medullary collecting ducts resulting in increased Na + and renal water excretion ( 170 , 171 ). Whether the potential benefits of proANP 31–67 extend to HFpEF is not established, although PGE2 has protective effects on the heart via enhancement of VEGF and eNOS expression levels and anti-inflammatory actions ( 172 , 173 ). Future studies are warranted to determine whether the cardiorenal protective effects and the cardiac function enhancing properties of these hormones can be explained by mechanisms different from cGMP activation.…”

LRRC15 expression indicates high level of stemness regulated by TWIST1 in mesenchymal stem cells

“…Mesenchymal stem cells (MSCs) are somatic stem cells present in various tissues including bone marrow, umbilical cord, and adipose tissue. 1 Because of its multiple differentiation potentials and ability to produce therapeutic cytokines such as transforming growth factor β (TGFB), interleukin (IL)-10, and IL-1 receptor antagonist (IL1RA), 2 , 3 MSCs are used in cell transplantation therapy for various diseases. On the other hand, method available to evaluate the MSC characteristics before undergoing cell transplantation is very limited.…”