Treatment with placental growth factor attenuates myocardial ischemia/reperfusion injury

Abstract

Studies have established that oxidative stress plays an important role in the pathology of myocardial ischemia/reperfusion injury (MIRI). Vascular endothelial growth factor receptor 1 (VEGFR1) activation was reported to reduce oxidative stress and apoptosis. In the present study, we tested the hypothesis that the activation of VEGFR1 by placental growth factor (PlGF) could reduce MIRI by regulating oxidative stress. Mouse hearts and neonatal mouse cardiomyocytes were subjected to ischemia/reperfusion (I/R) and oxygen glucose deprivation (OGD), respectively. PlGF pretreatment markedly ameliorated I/R injury, as demonstrated by reduced infarct size and improved cardiac function. The protection was associated with a reduction of cardiomyocyte apoptosis. Similarly, our in vitro study showed that PlGF treatment improved cell viability and reduced cardiomyocyte apoptosis. Also, activation of VEGFR1 by PlGF suppressed intracellular and mitochondrial reactive oxygen species (ROS) generation. However, VEGFR1 neutralizing monoclonal antibody, which preventing PlGF binding, totally blocked this protective effect. In conclusion, activation of VEGFR1 could protect heart from I/R injury by suppression of oxidative stress and apoptosis.

Causal association between placental growth factor and coronary heart disease: a Mendelian randomization study

“…They also confirmed that PlGF can inhibit the production of reactive oxygen species (ROS) in the mitochondria of cardiomyocytes after the activation of VEGFR1. Further studies showed that pretreatment with PlGF could activate the phosphorylation of Akt and GSK-3β and inhibit the activation of caspase-3 after reperfusion [ 23 ]. This shows that PlGF can activate VEGFR1 to protect the heart from ischaemia-reperfusion injury by inhibiting oxidative stress and reducing cardiomyocyte apoptosis.…”

Conditioned Medium from Human Amnion-Derived Mesenchymal Stromal/Stem Cells Attenuating the Effects of Cold Ischemia-Reperfusion Injury in an In Vitro Model Using Human Alveolar Epithelial Cells

“…Interestingly, Li et al reported that VEGF pathways activation is able to reduce oxidative stress and apoptosis [ 67 ]. Indeed, the treatment with PIGF-1 (aVEGFR-1 ligand) attenuates myocardial IRI by reducing both oxidative stress and apoptosis [ 68 ], while VEGF-D (a VEGFR-3 ligand) induces an antioxidant response of cells, which maintains the redox balance [ 69 ]. In addition, LIF has also been found to have protective effects against both oxidative stress and apoptosis [ 70 ].…”

The placenta and preeclampsia: villain or victim?

“…70 Although PlGF is known to be mainly secreted by the placenta in pregnancy, its putative role is cardiac protection from myocardial ischemia secondary to circulatory overload. 71 A recent study demonstrated that third-trimester assessment of cardiac function-specifically LVMI and E/e 0 ratio-was superior to clinical PE risk stratification using sFlt-1 and PlGF in screening for the development of PE at term. 38 The authors appropriately speculate that more aggressive blood pressure treatment in identified high-risk women could modify the maternal cardiac adaptation and prevent the development of late-onset PE and potentially reduce the risk of developing severe hypertension and organ damage later in life.…”