Revascularization of damaged tissue is a necessary part of wound healing. With unregulated or insufficient vessel growth, healing is delayed or pathological. Angiogenesis is regulated by expression of a variety of vascular growth factors and modulators, the most widely expressed and critical of which is vascular endothelial growth factor (VEGF). This protein is secreted by tissues in response to ischemic and inflammatory stimuli and results in endothelial migration, proliferation, and increased vascular permeability. The regulation of VEGF expression during wound healing is of considerable importance since angiogenesis appears to be disturbed in abnormally healing wounds. This paper describes the current state of knowledge of VEGF expression in wounds, regulation of expression, control of isoform specificity, and the effects of VEGF expression on blood vessels as they grow in wound healing, as understood from many different pathological paradigms.

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OBJECTIVE To investigate the effect of sustained hyperhomocysteinaemia (HHCy) on cavernosal smooth muscle function in a rabbit model of HHCy, developed using a methionine‐enriched diet in which cavernosal responses were characterized, as elevated plasma levels of homocysteine may be a risk factor for vasculogenic erectile dysfunction. MATERIALS AND METHODS Six New Zealand White rabbits were fed a diet supplemented with methionine (20 g/kg chow) for 4 weeks, while six control animals were fed a standard diet. Cavernosal strips were mounted in an organ bath and relaxation assessed when stimulated with carbachol, sodium nitroprusside (SNP), or noncholinergic, nonadrenergic (NANC)‐mediated relaxation to electrical‐field stimulation (EFS). Cavernosal tissue cGMP levels were assessed using an enzyme‐linked immunosorbent assay, and superoxide (O2·−) production assessed using an assay of the superoxide dismutase (SOD)‐inhibitable reduction of ferricytochrome c. RESULTS The methionine‐rich diet led to an early but sustained HHCy; cavernosal strips from animals after 4 weeks of HHCy had a significantly impaired relaxation response to carbachol, an index of endothelium‐dependent nitric oxide (NO)‐mediated relaxation. This impairment was reversed by incubating with either SOD or catalase. Relaxation with either SNP, an index of endothelium‐independent NO‐mediated relaxation, or NANC‐mediated EFS‐induced relaxation, was unaffected by HHCy. There was a corresponding significant reduction in cavernosal cGMP levels (index of NO activity) in the HHCy group, with a more than five‐fold increase in cavernosal tissue O2·− production. CONCLUSION Supplementing the diet of rabbits with methionine for 4 weeks caused an early and sustained HHCy and promoted a marked inhibitory effect on endothelium‐dependent relaxation and NO formation in isolated corpus cavernosum, an effect mediated by reactive oxygen species.