Topical simvastatin significantly accelerates wound healing in mice and may be a good treatment option for diabetic patients with nonhealing wounds, say researchers.
"We know that there are several factors involved in delayed wound healing in diabetes," said investigator Jun Asai (Kyoto Prefectural University of Medicine, Kawaramachi, Japan) in a press statement.
"These factors include more rapid apoptosis (cell death) and reduced angiogenesis (growth of new blood vessels). Impaired lymphangiogenesis, or formation of new lymphatic vessels, has also recently been established as a major factor," he added.
Writing in the American Journal of Pathology, the team compared topical application of simvastatin with petroleum jelly to full thickness wounds on the back of diabetic mice. Application of either the drug or placebo was repeated on days 4, 7 and 10.
Two weeks after the first treatment application, 90% of the simvastatin treated wounds had healed completely compared with less than 80% of those in the placebo group. The team noted the greatest effect after 7 days, at which point 79% and 52% of the simvastatin- and placebo-treated wounds had healed, respectively.
The researchers found that lymphangiogenesis and angiogenesis were higher in the wounds treated with simvastatin than with placebo, which may explain the accelerated healing.
"Our results suggested to us that the mechanisms underlying the lymphangiogenic effects of simvastatin in lymphatic endothelial cells (LECs) might be similar to those for angiogenic effects," commented Asai.
"However, contrary to our expectation, simvastatin did not promote proliferation of human LECs in vitro. We therefore investigated other possible sources of lymphangiogenic factors."
Instead, Asai and colleagues found that a greater number of infiltrating macrophages, resulting in a greater production of vascular endothelial growth factor C, were observed in simvastatin-treated wounds compared with those treated with placebo.
"Our observations suggest that the favorable effects of simvastatin on lymphangiogenesis are due both to a direct influence on lymphatics and indirect effects via macrophages homing to the wound," said Asai.
"This is a simple strategy that may have significant therapeutic potential for enhancing wound healing in patients with impaired microcirculation, such as that in diabetes."
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