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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 in vivo. A conditional knockout of AM in endothelial cells (AM EC-KO) was used. The amount of vascularization the matrigel implants was lower in AM EC-KO mice indicating a defective angiogenesis. Moreover, ablation of AM in endothelial cells revealed increased vascular permeability in comparison with wildtype 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 wild type 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE84345 | GEO | 2016/08/14

SECONDARY ACCESSION(S): PRJNA328969

REPOSITORIES: GEO

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Lack of adrenomedullin in mouse endothelial cells results in defective angiogenesis, enhanced vascular permeability, less metastasis, and more brain damage

Project description: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 in vivo. A conditional knockout of AM in endothelial cells (AM EC-KO) was used. The amount of vascularization the matrigel implants was lower in AM EC-KO mice indicating a defective angiogenesis. Moreover, ablation of AM in endothelial cells revealed increased vascular permeability in comparison with wildtype 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 wild type 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. Lung endothelial mRNA profiles of wild type (WT) and adrenomedullin endothelial cell conditional knockout (AM EC-KO) mice were generated by deep sequencing using Illumina GAIIx.

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