title: The renin-angiotensin system, bone marrow and progenitor cells.
abstract: Modulation of the RAS (renin-angiotensin system), in particular of the function of the hormones AngII (angiotensin II) and Ang-(1-7) [angiotensin-(1-7)], is an important target for pharmacotherapy in the cardiovascular system. In the classical view, such modulation affects cardiovascular cells to decrease hypertrophy, fibrosis and endothelial dysfunction, and improves diuresis. In this view, excessive stimulation of AT(1) receptors (AngII type 1 receptors) fulfils a detrimental role, as it promotes cardiovascular pathogenesis, and this is opposed by stimulation of the AT(2) receptor (angiotensin II type 2 receptor) and the Ang-(1-7) receptor encoded by the Mas proto-oncogene. In recent years, this view has been broadened with the observation that the RAS regulates bone marrow stromal cells and stem cells, thus involving haematopoiesis and tissue regeneration by progenitor cells. This change of paradigm has enlarged the field of perspectives for therapeutic application of existing as well as newly developed medicines that alter angiotensin signalling, which now stretches beyond cardiovascular therapy. In the present article, we review the role of AngII and Ang-(1-7) and their respective receptors in haematopoietic and mesenchymal stem cells, and discuss possible pharmacotherapeutical implications.
authors.affiliation: Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Matej
authors.initials: M
authors.lastname: Durik
authors.forename: Bruno
authors.initials: B
authors.lastname: Sevá Pessôa
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: Roks
mesh_terms: D050156:Adipogenesis; D000803:Angiotensin I / Q000502:physiology*; D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D004920:Erythropoiesis / Q000502:physiology; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000254:growth & development; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D024821:Metabolic Syndrome / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000502:physiology; D010446:Peptide Fragments / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; C000715470:MAS1 protein, human; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043562:Receptors, G-Protein-Coupled; D013777:Tetrazoles; D000804:Angiotensin II; D000068756:Valsartan; D000803:Angiotensin I; D014633:Valine; C118790:angiotensin I (1-7)