title: Increased aortic intimal proliferation due to MasR deletion in vitro.
abstract: A growing body of evidence suggests that the vascular actions of Ang-(1-7) appear to involve increased production of nitric oxide (NO), an important vasodilator, through the activation of MasR, thus indicating the involvement of the MasR in preventing endothelial dysfunction. However, it is unknown whether the MasR could be involved in the progression of the next step in atherosclerosis, neo-intimal formation. To determine whether the deletion of the MasR is involved in the development of intimal thickening in an in vitro model. Mice [three background controls (C57Bl/6) and 3 MasR (-/-)] were killed and the aortas excised and cleaned of connective tissue and cut into 3 mm rings. Rings were placed in an organ culture medium for 5 weeks, embedded in paraffin, cut at 5 μm and stained with haematoxylin and eosin and Masson's trichrome. In addition, aortic reactivity was measured in organ baths. After 5 weeks of culture, the intima:media ratio increased in the aortas from MasR (-/-) mice compared to the control group by 4.5-fold (P < 0.01). However, no significant difference in nuclei area count (cell proliferation) between the MasR (-/-) mice and control group was observed (0.87 ± 0.29% vs. 0.94 ± 0.18%, respectively, P = ns). Functional studies showed only a minor vasoconstrictive and full vasodilative response. This study shows that the deletion of the MasR causes marked increase in the aortic intima:media ratio, which is not due to generalized cellular proliferation. These results provide a functional role for the MasR in atherogenesis.
authors: The Centre for Chronic Disease Prevention & Management (CCDPM), Western CHRE, Victoria University, St Albans, Vic., Australia.
authors: Hiba
authors: H
authors: Alsaadon
authors: Department of Cardiovascular Diseases, International Clinical Research Center, St. Anne's University Hospital and Masaryk University, Brno, Czech Republic.
authors: Peter
authors: P
authors: Kruzliak
authors: The Centre for Chronic Disease Prevention & Management (CCDPM), Western CHRE, Victoria University, St Albans, Vic., Australia.
authors: Arthur
authors: A
authors: Smardencas
authors: The Centre for Chronic Disease Prevention & Management (CCDPM), Western CHRE, Victoria University, St Albans, Vic., Australia.
authors: Alan
authors: A
authors: Hayes
authors: Max-Delbrück-Center for Molecular Medicine, Berlin-Buch, Germany.
authors: Michael
authors: M
authors: Bader
authors: Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Vic., Australia.
authors: Peter
authors: P
authors: Angus
authors: Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Vic., Australia.
authors: Chandana
authors: C
authors: Herath
authors: The Centre for Chronic Disease Prevention & Management (CCDPM), Western CHRE, Victoria University, St Albans, Vic., Australia.
authors: Anthony
authors: A
authors: Zulli
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D049109:Cell Proliferation; D017353:Gene Deletion; D005838:Genotype; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058426:Neointima; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors; D046509:Tissue Culture Techniques; D014661:Vasoconstriction; D014664:Vasodilation
chemical_list: D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled
keywords: angiotensin (1-7) Mas receptor; atherosclerosis; endothelial function; intimal thickening