title: Angiogenesis and hypertension: the dual role of anti-hypertensive and anti-angiogenic therapies.
abstract: Essential hypertension may be a consequence of structural and functional alterations of the microvascular network growth resulting partly from abnormal regulation of vascular endothelial growth factor (VEGF), one of the most potent known angiogenic factors. As data from clinical trials on anti-VEGF drugs are becoming available, it is increasingly recognized that VEGF, in addition to being a proliferation and migration factor, is also a maintenance and protection factor for endothelial cells, whose altered regulation may cause a disturbance of vascular homeostasis. Elevated VEGF levels in hypertensive patients were shown to correlate with cardiovascular risk, early microvascular and target organ damage; accordingly treatment of hypertension significantly reduced VEGF levels. Recently and in agreement with the theory that impaired angiogenesis can contribute to increased peripheral resistance and raised blood pressure (BP), an involvement of VEGF gene promoter polymorphisms in the pathophysiology of hypertension has been hypothesized. In the last decade, anti-VEGF drugs have been used in clinical practice, especially in the oncology field. This review will summarize the present understanding of the contribution of VEGF to neoangiogenesis in hypertension and its possible role as a marker of vascular damage. Given the well established effects that antihypertensive drugs exert on the vasculature beyond BP lowering (pleiotropic effects), we will also discuss the effects of antihypertensive treatment on circulating VEGF levels. The biological mechanism and clinical impact of hypertensive complications during anti-angiogenic treatments will also be reviewed.
authors.affiliation: Department of Laboratory Medicine & Advanced Biotechnologies, IRCCS San Raffaele, Via della Pisana 235, Rome, Italy. patrizia.ferroni@sanraffaele.it
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferroni
authors.forename: David
authors.initials: D
authors.lastname: Della-Morte
authors.forename: Raffaele
authors.initials: R
authors.lastname: Palmirotta
authors.forename: Tatjana
authors.initials: T
authors.lastname: Rundek
authors.forename: Fiorella
authors.initials: F
authors.lastname: Guadagni
authors.forename: Mario
authors.initials: M
authors.lastname: Roselli
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D019317:Evidence-Based Medicine; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D058990:Molecular Targeted Therapy / Q000009:adverse effects; D009389:Neovascularization, Pathologic / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000959:Antihypertensive Agents; D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor