High-molecular-weight hyaluronic acid promotes the protective axis of the renin-angiotensin-aldosterone system in human dermal fibroblasts.

BACKGROUND

Hypertrophic scar and keloids are skin conditions strongly influenced by an imbalance of the renin-angiotensin-aldosterone system (RAAS). These disorders affect mainly African, Asian, and Spanish populations, and current treatments may not yield adequate results. This study aimed to demonstrate the RAAS modulation capacity of high-molecular-weight hyaluronic acid (HMWHA) in dermal fibroblasts.

METHODS

Renin, Angiotensin-converting enzyme (ACE), and Angiotensin-converting enzyme 2 (ACE2) activities were assessed fluorometrically after treating cells with ACE inhibitors (captopril or enalapril) or HMWHA (linear or BDDE cross-linked, a biomaterial widely used as a human dermal filler), administered either alone or in combination.

RESULTS

After 120 min treatment, the greatest reductions in renin and ACE activities were obtained with CHA-S (53.76 ± 15.51 nmol/min/mg) and HA-S (0.051 ± 0.013 nmol/min/mg), respectively. ACE2 activity, however, had its largest increase with Ena (75.49 ± 11.49 nmol/min/mg). The ACE2/ACE ratio, for the same treatment period, was greatly increased for both Ena and HA-S (923.1 ± 178.7; 1209 ± 287.0, respectively).

CONCLUSION

This study demonstrated that HMWHA promotes the protective axis of RAAS, with known anti-inflammatory and anti-fibrotic effects, by enhancing ACE2 activity and reducing ACE activity, opening perspectives for therapeutic approaches targeting cicatricial alterations and inflammatory and fibrotic dermal diseases.