Cerebral Ischemia and Angiogenesis

Abstract

Angiogenesis occurs in a wide range of conditions. As ischemic tissue usually depends on collateral blood flow from newly produced vessels, acceleration of angiogenesis should be of therapeutic value to ischemic disorders. Indeed, therapeutic angiogenesis reduced tissue injury in myocardial or limb ischemia. In ischemic stroke, on the other hand, angiogenic factors often increase vascular permeability and thus may deteriorate tissue damage. In order to apply safely the therapeutic angiogenesis for ischemic stroke treatment, elucidating precise mechanism of brain angiogenesis is mandatory. In the present article, we review previous reports which investigated molecular mechanisms of angiogenesis. Endothelial cell mitogens, enzymes that degrade surrounding extracellular matrix, and molecules implicated in endothelial cells migration are induced rapidly in the ischemic brain. Their possible neuroprotective or injury exacerbating effects are discussed. Because therapeutic potential of angiogenic factors application had gained much attention, we here extensively reviewed relevant previous reports. In the future however, there is a need to consider angiogenesis in relation with regenerative medicine, as angiogenic factors sometimes possess neuron producing property.

The Role of Endothelial Progenitor Cells in Ischemic Cerebral and Heart Diseases

“…, which is generally compatible with the definitions of several other investigators secretion is induced by ischemia (37,38).…”

“…In order to safely apply therapeutic angiogenesis for ischemic stroke treatment, elu-CD133 + cells, as an EPC-enriched population, provided a marker of cerebrovascular function (93). They demoncidating its precise mechanism is mandatory (37). Upregulation and increased phosphorylation of eNOS strated that circulating EPCs increased after the onset of improves endothelium-dependent vasodilation (35,48).…”

“…sprout, and make new lumen (37). In angiogenesis, periexpress CD133 and c-kit (CD117), whereas CESs do not.…”

Vascular Endothelial Cell-specific MicroRNA-15a Inhibits Angiogenesis in Hindlimb Ischemia

“…Extensive studies have shown that post-ischemic angiogenesis plays a crucial role in the recovery of blood flow in affected tissue (45)(46)(47). Thus, angiogenic vessels in the ischemic boundary zone may contribute to recovery of tissue at risk by restoring metabolism in surviving neurons or cardiomyocytes as well as provide the essential trophic support to newly generated neuronal or cardiac cells.…”

Long-Term Neuroblast Migration Along Blood Vessels in an Area With Transient Angiogenesis and Increased Vascularization After Stroke

“…10 Stroke leads to angiogenesis in the ischemic hemisphere and peri-infarct area. 11 This area is hypoxic, which probably triggers angiogenesis through the vascular endothelial growth factor system. 12 Neuroblasts migrate in association with blood vessels in the mouse striatum during the first weeks after stroke.…”