Angiogenesis: basic pathophysiology and implications for disease

The development of new blood vessels is essential to embryonic growth and throughout life for physiological repair processes such as wound healing, post-ischaemic tissue restoration, and the endometrial changes of the menstrual cycle. However, abnormal development of new blood vessels has been implicated in numerous pathophysiological processes. For example, inhibited growth of blood vessels is associated with bowel atresia and peptic ulcers.1–3 Furthermore, although generally focussing on tumour growth, increased vascular growth has been demonstrated in many other non-malignant diseases such rheumatoid arthritis, systemic lupus erythematosus, psoriasis, proliferative retinopathy and atherosclerosis.3–5 It is therefore clear that the subject is currently attracting considerable research energies as tools are becoming available to assess possible therapeutic options. The formation of the vascular system is fashioned by three processes. During embryogenesis, there is differentiation of embryonic mesenchymal cells (the endothelial precursor cells or angioblasts) into endothelial cells resulting in de novo development of blood vessels (vasculogenesis).6 Secondly, angiogenesis refers to the formation of new blood vessels by sprouting from pre-existing small vessels in adult and embryonic tissue (sprouting angiogenesis) or by intravascular subdivision (intussusception). The existing vasculature can betransformed into a mature network by processes of pruning and remodelling. Thirdly, arteriogenesisis defined as rapid proliferation of pre-existingcollateral vessels.7 Angiogenesis also seems to bean organ-specific process reliant on the stage of microvascular network.8 Since angiogenesis seems to play a key role inthe pathophysiology of various disease processes,recent attempts have been made to utilize this knowledge in the development of new therapeutic approaches. For example, inhibition of angiogenesis has been used in the restriction of tumour growth and the seeding of metastases, as well asin rheumatoid arthritis, where an aim is to reduce the infiltration of inflammatory cells and soluble mediators.9–11 Angiogenesis related research in cardiovascular medicine has initially been …