Fibroblast Angiotensin II type 1a receptors contribute to Angiotensin II-induced medial hyperplasia in the ascending aorta

Aruna Poduri, Debra L. Rateri, Deborah A. Howatt, Anju Balakrishnan, Jessica J. Moorleghen, Lisa A. Cassis, Alan Daugherty

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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. Approach and 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.

Original languageEnglish
Pages (from-to)1995-2002
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume35
Issue number9
DOIs
StatePublished - Sep 28 2015

Bibliographical note

Publisher Copyright:
© 2015 American Heart Association, Inc.

Keywords

  • angiotensin II
  • angiotensin II type 1 receptor
  • endothelium
  • fibroblasts
  • medial thickening
  • smooth muscle

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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