Research Paper Volume 7, Issue 12 pp 1185—1197

Knockout of Angiotensin AT2 receptors accelerates healing but impairs quality

Mahya Faghih 1, , Sayed M Hosseini 2, , Barbara Smith 3, , Amir Mehdi Ansari 2, , Frank Lay 2, , Ali Karim Ahmed 2, , Tedashi Inagami 4, , Guy P Marti 2, , John W Harmon 2, , Jeremy D Walston 1, , Peter M Abadir 1, ,

  • 1 Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA
  • 2 Department of Surgery and Hendrix Burn/Wound Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA
  • 3 Cell Biology Imaging Facility, Johns Hopkins University School of Medicine Baltimore, MD 21224, USA
  • 4 Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA

received: December 4, 2015 ; accepted: December 2, 2015 ; published: December 31, 2015 ;

https://doi.org/10.18632/aging.100868
How to Cite

Abstract

Wounds are among the most common, painful, debilitating and costly conditions in older adults. Disruption of the angiotensin type 1 receptors (AT1R), has been associated with impaired wound healing, suggesting a critical role for AT1R in this repair process. Biological functions of angiotensin type 2 receptors (AT2R) are less studied. We investigated effects of genetically disrupting AT2R on rate and quality of wound healing. Our results suggest that AT2R effects on rate of wound closure depends on the phase of wound healing. We observed delayed healing during early phase of wound healing (inflammation). An accelerated healing rate was seen during later stages (proliferation and remodeling). By day 12, fifty percent of AT2R−/− mice had complete wound closure as compared to none in either C57/BL6 or AT1R−/− mice. There was a significant increase in AT1R, TGFβ1 and TGFβ2 expression during the proliferative and remodeling phases in AT2R−/− mice. Despite the accelerated closure rate, AT2R−/− mice had more fragile healed skin. Our results suggest that in the absence of AT2R, wound healing rate is accelerated, but yielded worse skin quality. Elucidating the contribution of both of the angiotensin receptors may help fine tune future intervention aimed at wound repair in older individuals

Abbreviations

Ang II: angiotensin II; AT1R: Angiotensin II type 1 receptors; AT2R: Angiotensin II type 2 receptors; AT1R−/−: Angiotensin II type 1 receptors knockout; AT2R−/−: Angiotensin II type 2 receptors knockout; TGFβ: transforming growth factor-β.

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