Vascular endothelial growth factors (VEGFs) and stroke

Abstract

Vascular endothelial growth factors (VEGFs) have been shown to participate in atherosclerosis, arteriogenesis, cerebral edema, neuroprotection, neurogenesis, angiogenesis, postischemic brain and vessel repair, and the effects of transplanted stem cells in experimental stroke. Most of these actions involve VEGF-A and the VEGFR-2 receptor, but VEGF-B, placental growth factor, and VEGFR-1 have been implicated in some cases as well. VEGF signaling pathways represent important potential targets for the acute and chronic treatment of stroke.

Fig. 1

VEGF-A and atherosclerosis. Hypoxia and inflammation in the atherosclerotic plaque trigger VEGF-A expression in vascular smooth muscle cells (VSMC) and macrophages. VEGF-A, in turn, acts on vasa vasorum to promote angiogenesis, which may be associated with hemorrhage, and promotes migration of VSMC from the tunica media of the vessel wall into the plaque

Fig. 2

VEGF effects in acute ischemic stroke. A horizontal section of the human brain shows an acute infarct within the territory of the middle cerebral artery (dotted line). VEGF-A is induced in the ischemic border zone and acts on local neurons and endothelial cells to promote neuroprotection (green arrow) and angiogenesis (red arrow). VEGF-A also stimulates neurogenesis (blue arrow) in the subventricular zone, from which new neurons migrate to the site of ischemia. Other VEGF family members, including VEGF-B and PlGF, share some of these effects

Fig. 3

VEGF-A-mediated postischemic repair. VEGF-A appears to be a mediator of postischemic brain and vessel repair. Following cerebral infarction (blue) due to arterial occlusion (asterisk), VEGF-A expression is increased (thick arrow, top left) in nonischemic brain regions that exhibit remote plasticity (pink); VEGF-A acting here (thin arrow, top left) may help to restore brain function. Increased serum VEGF-A levels after stroke (thick arrow, bottom right) also mobilize endothelial progenitor cells (EPCs, green) from the bone marrow, enhancing repair of ischemia-damaged vessels (thin arrows, bottom right)