{'fraction_non_alphanumeric': 0.016427822439706398, 'fraction_numerical': 0.005941978329255505, 'mean_word_length': 5.640371229698376, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Angiogenesis and the Heart: Therapeutic Implications

The phenomenon of angiogenesis-the growth of capillary blood vessels and the development of new blood vesselshas been familiar to morphologists and physiologists since the late 19th century. Most of the early research revolved around tumour neovascularization and was initiated by Goldman who published a key paper in 19071. The pioneering work of Folkman began in the early 1960s and was directed mainly at elucidating the mechanisms of early tumour angiogenesis2. Under normal conditions, angiogenesis is highly regulated and occurs when an imbalance exists between the supply and demand of oxygen and nutrients to a vascular bed, or if inflammation is present. Initially the concept of angiogenesis was resisted, because tumour hypervascularity was believed to result from dilatation of pre-existing host vessels rather than growth and development of vessels de novo. Opinions changed, however, when avascular rabbit corneas were seen to acquire new vessels when implanted with tumours; and these studies eventually led to the isolation and purification of an angiogenic factor from tumour cells3. For a time it was thought that angiogenic initiating factors must be endothelial mitogens. Basic fibroblast growth factor (b-FGF), first purified by Shing and Folkman, is an endothelial mitogen4; but the next angiogenic factor to be discovered, angiogenin, was not5. Whereas Folkman6 and his associates were instrumental in establishing the basic mechanisms of tumour vessel growth and development, it was Schaper who greatly increased our understanding of angiogenesis in the heart and the development of the coronary collateral circulation7. Since the work of these early investigators, the advent of recombinant technology and the development of novel drug delivery and biocompatible systems to deliver peptides have increased the potential for both scientific investigation and therapeutic angiogenesis. The fact that collateral vessels develop and grow during gradual coronary occlusion in animal models and in patients, along with the observation that certain mitogenic growth factors and cytokines can induce angiogenesis, suggests that angiogenic substances could be of value in the treatment of occlusive coronary artery disease. Currently, myocardial ischaemia and its consequences can be treated with coronary artery bypass grafting (CABG), percutaneous transluminal coronary angioplasty (PTCA), and more recently with transmyocardial laser revascularization (TMLR). However, a subset of patients exists who are not candidates for CABG, PTCA or other conventional methods of revascularization. The lack of efficacy and hazards of TMLR leave a void that may be filled by other approaches such as therapeutic angiogenesis. Here we discuss the potential mechanisms and the therapeutic implications.