title: Fibroblast Angiotensin II Type 1a Receptors Contribute to Angiotensin II-Induced Medial Hyperplasia in the Ascending Aorta.
abstract: OBJECTIVE
  Angiotensin II (Ang II) infusion causes aortic medial thickening via stimulation of angiotensin II type 1a (AT1a) receptors. The purpose of this study was to determine the cellular loci of AT1a receptors that mediate this Ang II-induced aortic pathology.
  
  
  RESULTS
  Saline or Ang II was infused into AT1a receptor floxed mice expressing Cre under control of cell-specific promoters. Initially, AT1a receptors were depleted in aortic smooth muscle cell and endothelium by expressing Cre under control of SM22 and Tie2 promoters, respectively. Deletion of AT1a receptors in either cell type had no effect on Ang II-induced medial thickening. To determine whether this effect was related to neural stimulation, AT1a receptors were depleted using an enolase 2-driven Cre. Depletion of AT1a receptors in neural cells attenuated Ang II-induced medial thickening of the ascending, but not descending aorta. Lineage tracking studies, using ROSA26-LacZ, demonstrated that enolase 2 was also expressed in adventitial cells adjacent to the region of attenuated thickening. To determine whether adventitial fibroblasts contributed to this attenuation, AT1a receptors in fibroblasts were depleted using S100A4 driven Cre. Similar to enolase 2-Cre, Ang II-induced medial thickening was attenuated in the ascending, but not the descending aorta. Lineage tracking demonstrated an increase of S100A4-LacZ positive cells in the media of the ascending region during Ang II infusion.
  
  
  CONCLUSIONS
  AT1a receptor depletion in fibroblasts attenuates Ang II-induced medial hyperplasia in the ascending aorta.
authors.affiliation: From the Saha Cardiovascular Research Center (A.P., D.L.R., D.A.H., A.B., J.J.M., A.D.) and Department of Molecular and Biomedical Pharmacology (L.A.C.), University of Kentucky, Lexington.
authors.forename: Aruna
authors.initials: A
authors.lastname: Poduri
authors.affiliation: From the Saha Cardiovascular Research Center (A.P., D.L.R., D.A.H., A.B., J.J.M., A.D.) and Department of Molecular and Biomedical Pharmacology (L.A.C.), University of Kentucky, Lexington.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Rateri
authors.affiliation: From the Saha Cardiovascular Research Center (A.P., D.L.R., D.A.H., A.B., J.J.M., A.D.) and Department of Molecular and Biomedical Pharmacology (L.A.C.), University of Kentucky, Lexington.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Howatt
authors.affiliation: From the Saha Cardiovascular Research Center (A.P., D.L.R., D.A.H., A.B., J.J.M., A.D.) and Department of Molecular and Biomedical Pharmacology (L.A.C.), University of Kentucky, Lexington.
authors.forename: Anju
authors.initials: A
authors.lastname: Balakrishnan
authors.affiliation: From the Saha Cardiovascular Research Center (A.P., D.L.R., D.A.H., A.B., J.J.M., A.D.) and Department of Molecular and Biomedical Pharmacology (L.A.C.), University of Kentucky, Lexington.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Moorleghen
authors.affiliation: From the Saha Cardiovascular Research Center (A.P., D.L.R., D.A.H., A.B., J.J.M., A.D.) and Department of Molecular and Biomedical Pharmacology (L.A.C.), University of Kentucky, Lexington.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cassis
authors.affiliation: From the Saha Cardiovascular Research Center (A.P., D.L.R., D.A.H., A.B., J.J.M., A.D.) and Department of Molecular and Biomedical Pharmacology (L.A.C.), University of Kentucky, Lexington. Alan.Daugherty@uky.edu.
authors.forename: Alan
authors.initials: A
authors.lastname: Daugherty
mesh_terms: D000804:Angiotensin II / Q000633:toxicity; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D005838:Genotype; D006965:Hyperplasia / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D007262:Infusions, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics*; D044140:Receptor, Angiotensin, Type 1 / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D017540:Tunica Media / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D004247:DNA
keywords: angiotensin II; angiotensin II type 1 receptor; endothelium; fibroblasts; medial thickening; smooth muscle