title: Lack of adrenomedullin in mouse endothelial cells results in defective angiogenesis, enhanced vascular permeability, less metastasis, and more brain damage.
abstract: Adrenomedullin (AM) is a vasodilating peptide involved in the regulation of circulatory homeostasis and in the pathophysiology of certain cardiovascular diseases. AM plays critical roles in blood vessels, including regulation of vascular stability and permeability. To elucidate the autocrine/paracrine function of AM in endothelial cells (EC) in vivo, a conditional knockout of AM in EC (AM(EC-KO)) was used. The amount of vascularization of the matrigel implants was lower in AM(EC-KO) mice indicating a defective angiogenesis. Moreover, ablation of AM in EC revealed increased vascular permeability in comparison with wild type (WT) littermates. In addition, AM(EC-KO) lungs exhibited significantly less tumor growth than littermate WT mice using a syngeneic model of metastasis. Furthermore, following middle cerebral artery permanent occlusion, there was a significant infarct size decrease in animals lacking endothelial AM when compared to their WT counterparts. AM is an important regulator of EC function, angiogenesis, tumorigenesis, and brain response to ischemia. Studies of AM should bring novel approaches to the treatment of vascular diseases.
authors.affiliation: Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), C/Piqueras 98, 26006-Logroño. Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Ochoa-Callejero
authors.affiliation: Neurovascular Research Group, Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute, Av. Doctor Arce 37, 28002-Madrid. Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pozo-Rodrigálvarez
authors.affiliation: Neurovascular Research Group, Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute, Av. Doctor Arce 37, 28002-Madrid. Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Martínez-Murillo
authors.affiliation: Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), C/Piqueras 98, 26006-Logroño. Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Martínez
mesh_terms: D053607:Adrenomedullin / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology; D002199:Capillary Permeability; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology; D008175:Lung Neoplasms / Q000556:secondary*; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic
chemical_list: D053607:Adrenomedullin