Knockout of Angiotensin AT(2) receptors accelerates healing but impairs quality

Wounds are among the most common, painful, debilitating and costly conditions in older adults. Disruption of the angiotensin type 1 receptors (AT(1)R), has been associated with impaired wound healing, suggesting a critical role for AT(1)R in this repair process. Biological functions of angiotensin type 2 receptors (AT(2)R) are less studied. We investigated effects of genetically disrupting AT(2)R on rate and quality of wound healing. Our results suggest that AT(2)R 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 AT(2)R(−/−) mice had complete wound closure as compared to none in either C57/BL6 or AT(1)R(−/−) mice. There was a significant increase in AT(1)R, TGFβ(1) and TGFβ(2) expression during the proliferative and remodeling phases in AT(2)R(−/−) mice. Despite the accelerated closure rate, AT(2)R(−/−) mice had more fragile healed skin. Our results suggest that in the absence of AT(2)R, 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.