Angiogenic growth factors and hypertension.
Emerging evidence supports a novel view of hypertension as a disease of inadequate or aberrant responses to angiogenic growth factors (AGF). Patients with hypertension have reduced microvascular density, with some evidence supporting a primary role for rarefaction in causing hypertension. Two clinical models have demonstrated a link between inhibition of AGF activity and hypertension. A major side effect of bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF), is hypertension. Pre-eclampsia is accompanied by high circulating levels of soluble VEGF receptor-1, which forms inactive complexes with VEGF and placental growth factor (PlGF). Paradoxically, early studies have demonstrated high circulating levels of AGF in hypertension. Several mechanisms may account for this finding including increased vascular stretch, tissue ischemia, compensatory responses, decreased clearance or a combination of these mechanisms. High AGF in hypertension could contribute to clinical sequelae such as peripheral and pulmonary edema, microalbuminuria, and progression of atherosclerosis. However, a role for altered angiogenesis in the pathogenesis of hypertension or its sequelae has not been established. Novel studies to understand the roles of AGF in hypertensive patients are warranted.
Sane
David C
DC
Department of Internal Medicine, Section of Cardiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1045, USA. dsane@wfubmc.edu
Anton
Lauren
L
Brosnihan
K Bridget
KB
D042501:Angiogenic Proteins / Q000502:physiology*; D000818:Animals; D005260:Female; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism; D007610:Kallikreins / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic; D011225:Pre-Eclampsia / Q000503:physiopathology; D011247:Pregnancy; D012084:Renin-Angiotensin System / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
D042501:Angiogenic Proteins; D042461:Vascular Endothelial Growth Factor A; D007610:Kallikreins