Therapeutic targeting of the angiopoietin-TIE pathway.

The endothelial angiopoietin (ANG)-TIE growth factor receptor pathway regulates vascular permeability and pathological vascular remodelling during inflammation, tumour angiogenesis and metastasis. Drugs that target the ANG-TIE pathway are in clinical development for oncological and ophthalmological applications. The aim is to complement current vascular endothelial growth factor (VEGF)-based anti-angiogenic therapies in cancer, wet age-related macular degeneration and macular oedema. The unique function of the ANG-TIE pathway in vascular stabilization also renders this pathway an attractive target in sepsis, organ transplantation, atherosclerosis and vascular complications of diabetes. This Review covers key aspects of the function of the ANG-TIE pathway in vascular disease and describes the recent development of novel therapeutics that target this pathway.

The airway vasculature: recent advances and clinical implications.

It is increasingly recognised that the airway circulation plays an important role in airway diseases, either through a change in blood flow or through microvascular leakage. Most of the information available regarding the anatomy and physiology of bronchial blood flow and its regulation has necessarily derived from animal studies. However, there have recently been important advances in understanding airway blood flow in airway disease in humans through the development of non-invasive methods and in the quantification of microvascular leakage using plasma markers. These studies have shown that bronchial blood flow is increased in patients with asthma but not in those with chronic obstructive pulmonary disease, confirming previous pathology investigations. Changes in bronchial blood flow may in part reflect the generation of new vascular vessels, a process known as "angiogenesis" which is caused by airway inflammation. Angiogenesis and the resulting plasma leak affect airway physiology, drug clearance and its bioavailability. This review discusses the anatomy, physiology and regulation of bronchial blood flow in the normal and diseased lung, In addition, it analyses the effect of current medical treatment and discusses the potential use of new anti-angiogenesis medications. The development of non-invasive assessment of bronchial blood flow and the study of angiogenesis have provided a tool to investigate airway physiology in vivo; these advances will contribute to a better understanding of inflammatory airway diseases as well as the implication of these findings to management.