The always active, always clever lab team of Sawaya, Tomic-Canic and coworkers have yet another strong addition to the literature in press with the Journal of Clinical Investigation (JCI Insight). These authors investigated topical statins with respect to therapeutic potential to restore healing in patients with DFUs. Through next-generation sequencing on mevastatin-treated primary human keratinocytes, the study showed that the statin activated and modulated epidermal growth factor (EGF) signaling. This initiated an anti-proliferative and pro-migratory phenotype. These findings suggest that statins could shift the phenotype of a DFU in a similar way to stimulate healing.1
Additionally, mevastatin induced a migratory phenotype in primary human keratinocytes through EGF-mediated activation of Ras-related C3 botulinum toxin substrate (Rac1). This resulted in actin cytoskeletal reorganization and lamellipodia formation. The study authors found that the EGF receptor was downregulated in tissue biopsies from patients with DFUs. Mevastatin restored EGF signaling in DFUs through disruption of caveolae to promote keratinocyte migration, which was confirmed by caveolin-1 (Cav1) overexpression studies. The authors of this study concluded that topical statins may have therapeutic potential for DFUs.1
To our knowledge, no one is currently actively using topical statins for DFUs. This study merely indicates that the possibility is feasible. It is entirely plausible, though, that we will be working closely with our patients’ primary care physicians and cardiologists to not only ensure patients are on maximum medical therapy but determine whether topical statins could be beneficial as well in facilitating healing.
Dr. Armstrong is a Professor of Surgery at the Keck School of Medicine at the University of Southern California. He is the Director of the Southwestern Academic Limb Salvage Alliance (SALSA).
Editor’s Note: This blog originally appeared at:
https://diabeticfootonline.com/2019/11/03/can-topical-statins-improve-healing/. It is adapted with permission from the author.
- Sawaya AP, Jozic I, Stone RC, Tomic-Canic M, et al. Mevastatin promotes healing by targeting Caveolin-1 to restore EGFR signaling. JCI Insight. In press.