What Are the Promoters of Angiogenesis or Arteriogenesis?

There is increasing evidence that angiogenesis relies on hypoxia, whereas arteriogenesis does not. Hypoxia is known to transcriptionally upregulate the expression of vascular endothelial growth factor (VEGF), but posttranscriptional mRNA stabilization may be even more important. VEGF is able to circumvent the hypoxia-induced translation inhibition, and in a rabbit model of hindlimb ischemia, VEGF expression and capillary growth are indeed restricted to ischemic regions.

However, collateral artery growth (arteriogenesis) occurs in nonhypoxic tissue.7 Resting blood flow in the thigh muscles where collaterals develop after femoral artery occlusion is not decreased, its ATP and phosphocreatine content is normal, and hypoxia-induced gene transcription (LDH-A, VEGF) is not activated. The distance between ischemic regions and the predilection sites for collateral growth can be absurdly large: up to 70 cm between a patient's gangrenous big toe and collaterals spanning a femoral or popliteal ... more.

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