Angiotensin System Modulation in Wound Healing

The renin–angiotensin system, long recognised for its regulation of blood pressure and fluid balance, has emerged as a key modulator of cutaneous repair. Angiotensin II, acting through angiotensin II type 1 receptors (AT1R), promotes fibroblast and keratinocyte migration, stimulates transforming growth factor β1 (TGF-β1) signalling and drives collagen deposition. Conversely, blockade of AT1R or inhibition of angiotensin-converting enzyme (ACE) attenuates fibroblast proliferation, suppresses TGF-β1-mediated pathways and reduces scar formation, enhancing re-epithelialisation and neovascularisation. In parallel, activation of angiotensin II type 2 receptors (AT2R) has been shown to accelerate wound maturation, dampen inflammation and foster a more organised extracellular matrix. Recent advances focus on dual-target approaches that inhibit AT1R while stimulating AT2R, topical delivery of receptor modulators and bioactive compounds that fine-tune the balance between pro- and anti-fibrotic signals. Collectively, these strategies promise novel therapeutic avenues to improve healing outcomes and reduce pathological scarring.

Research from Nature Portfolio

Angiotensin-converting enzyme inhibitors have been demonstrated to inhibit both canonical (SMAD2/3) and non-canonical (TAK1) TGF-β1 pathways in rodent models. Treatment with ACE inhibitors reduced fibroblast proliferation, suppressed collagen and TGF-β1 expression in vitro, and in vivo yielded narrower scars with enhanced re-epithelialisation, neovascularisation and organised granulation tissue, suggesting clinical potential to mitigate fibrotic scarring.

Angiotensin System Modulation in Wound Healing publication trend

The graph below shows the total number of articles in angiotensin system modulation in wound healing across all publications each year (not limited to Nature Index journals).

Technical terms

Angiotensin-converting enzyme inhibitor (ACEI): A compound that prevents conversion of angiotensin I to angiotensin II, modulating downstream receptor signalling.

Angiotensin II type 1 receptor (AT1R): A G-protein-coupled receptor through which angiotensin II exerts pro-fibrotic and pro-inflammatory effects.

Angiotensin II type 2 receptor (AT2R): A receptor often counterbalancing AT1R actions, promoting anti-inflammatory and regenerative processes.

Re-epithelialisation: The process by which epidermal cells migrate and proliferate to restore skin continuity after injury.

Granulation tissue: Newly formed vascularised connective tissue that fills the wound bed during healing.

References

1. A strategy for selective screening of dual-target bioactive compounds against hypertrophic scar through inhibiting angiotensin II type 1 receptor while stimulating type 2 receptor from Chinese herbs. Chinese Medicine (2025).
2. AT2R Activation Improves Wound Healing in a Preclinical Mouse Model. Biomedicines (2024).
3. Angiotensin-converting enzyme inhibitor reduces scar formation by inhibiting both canonical and noncanonical TGF-β1 pathways. Scientific Reports (2018).
4. A Novel Function of Angiotensin II in Skin Wound Healing INDUCTION OF FIBROBLAST AND KERATINOCYTE MIGRATION BY ANGIOTENSIN II VIA HEPARIN-BINDING EPIDERMAL GROWTH FACTOR (EGF)-LIKE GROWTH FACTOR-MEDIATED EGF RECEPTOR TRANSACTIVATION*. Journal of Biological Chemistry (2006).