Ischemic vascular disease and solid cancers: opposing ends of the angiogenic spectrum?

Angiogenesis is a key pathway crucial to the patho-physiology of both vascular disease and solid cancer. In physiological conditions, a fine balance of pro- and anti-angiogenic factors is maintained as part of normal homeostatic mechanisms. It is widely accepted that excess angiogenesis influences the development or progression of tumours whilst insufficient angiogenesis may predispose to ischemic vascular disease. Although there are some factors, which predispose to both cancers and vascular disease, we believe there is a reasonable body of literature that suggests an inverse association between the two. We hypothesise that pro-angiogenic and anti-angiogenic phenotypes exist in the population. This may be due to a combination of underlying genetic variations and/or environmental factors. Pro-angiogenic phenotypes would have increased susceptibility to solid cancers and decreased predisposition to cardiovascular diseases and vice versa with the anti-angiogenic phenotypes. We propose that genetic and environmental factors causing a shift in the balance of angiogenesis will predispose individuals towards one group of pathologies while protecting them from another. Evaluation of this hypothesis will in the first instance involve carefully designed large population based observational studies to determine if an inverse relationship exists between the predisposition to ischemic vascular disease and the predisposition to solid cancer. Further detailed study of the pathways and underlying mechanisms of angiogenesis especially in disease states would facilitate better understanding of its regulation. Evaluation and validation of molecular markers that affect the 'angiogenesis pathway' may be helpful in determining the angiogenic potential of individual subjects. Determining where individuals lie along this spectrum may have a potential role in the prediction and stratification of risk of cancer and vascular disease. Modifying risk for patients at high risk of disease at the two opposing ends of the spectrum may then be possible by either lifestyle or dietary alterations or drugs targeting the angiogenic pathway.