Educational Forum - Hypertension, cancer and angiogenesis: Relevant epidemiological and pharmacological aspects

Hypertension and cancer are two leading diseases in the world. Often they coexist in patients. They share some common predisposing factors e.g., ageing, obesity, alcohol consumption and smoking habit. Abnormal angiogenesis (i.e. the formation of new blood vessels from an existing vasculature) is a common pathological feature, and some pro-angiogenic factors e.g., vascular endothelial growth factor, basic fibroblast growth factor, tumor necrosis factor-alpha and few interleukins are common mediators in both the conditions. Among these, the most important is vascular endothelial growth factor, a specific mitogen for vascular endothelium. It increases vascular permeability and induces proteolytic enzymes that are necessary for vascular remodeling. Monocyte/macrophages also have been shown to play a role in angiogenesis by releasing some of the above mediators. Angiogenesis is essential for the growth and metastasis of solid tumors. The essence of impaired angiogenesis (despite high level of angiogenic factors), probably due to signaling defects in the endothelium in hypertension, is not clearly understood. Some anticancer drugs e.g., taxanes, vinblastine, temozolomide and doxorubicin have antiangiogenic activity. Nevertheless, several classes of specific antiangiogenic agents are being evaluated for their anticancer effects and are emerging as new drugs for cancer treatment. COX-2 inhibitors (e.g., celecoxib and rofecoxib), neovastat, thalidomide analogues and some cytokine inhibitors also inhibit angiogenesis. Although certain antihypertensives are found to have antiangiogenic properties, some show pro-angiogenic activity. Also, a number of epidemiological studies have found an association between the use of antihypertensive drugs and risk of cancer. However, a better understanding of common cell biology and the relationship between hypertension and malignancy may be helpful in elucidating more preventive and therapeutic avenues to manage hypertension and cancer.