A double-edged sword effect of angiogenesis in hypertension: a review

Abstract

Hypertension, commonly known as high blood pressure, is a serious medical condition that significantly raises the risk of heart, brain, kidney, and blood vessel diseases. It remains one of the leading causes of morbidity and mortality worldwide, with its mechanisms still not fully understood. One emerging area of interest is the role of angiogenesis, the formation of new blood vessels, which is regulated by a delicate balance between pro- and anti-angiogenic modulators, including angiogenic factors, extracellular matrix proteins, adhesion receptors, and proteolytic enzymes. Disruption of this balance can lead to abnormal angiogenesis, potentially contributing to hypertension, as angiogenic growth factors are critical in maintaining vascular structure. If left untreated, high blood pressure damages capillaries and microvessels, accelerating the process of vascular rarefaction. Notably, microvascular rarefaction may occur independently of changes in blood pressure, indicating its potential role as a primary factor in hypertension progression. The ‘double-edged sword effect’ describes the paradoxical impact of both pro- and anti-angiogenic therapies, where either type of drug can induce hypertension, highlighting the dual nature of angiogenic regulation in vascular health. Given the rising use of angiogenesis-modulating therapies in treating various diseases, therapy-induced hypertension is expected to become more prevalent. This review was conducted to address the growing need to understand this dual effect of angiogenic therapies, the mechanisms underlying hypertension development, and the critical importance of early detection and long-term management of hypertension in patients undergoing such treatments.