5-Methoxytryptophan (5-MTP) is a metabolite of tryptophan metabolism. We recently demonstrated that 5-MTP protects against intimal hyperplasia in a mouse neointima formation model of left common carotid artery ligation. The novel protective function of 5-MTP is in part through reducing vascular smooth muscle cell proliferation and migration. In this study, we investigated the effect of 5-MTP on endothelial cell (EC) function in response to vascular injury. We subjected approximately 12 weeks old C57BL/6 mice to a femoral artery guide wire injury model to denude endothelium. Following surgery, mice were treated with vehicle (PBS) or 25 mg/kg of 5-MTP by intraperitoneal injection 3 times a week. Femoral arteries were harvested at early time points after injury for histological analysis to evaluate endothelium. CD31 staining revealed that endothelium was partially regenerated in the injured femoral arteries of vehicle-treated mice. In comparison, 5-MTP significantly increased endothelial regeneration in the injured arteries. Given that proinflammatory cytokine IL-1β and TNF-α are increased in the injured vessel wall, we next examined whether 5-MTP could protect against EC dysfunction induced by IL-1β or TNF-α. Interestingly, 5-MTP did not affect IL-1β or TNF-α-reduced EC proliferation. In contrast, 5-MTP ameliorates IL-1β-induced inflammatory cell adhesion and TNF-α-reduced EC migration. Taken together, our results suggest an important role of 5-MTP on EC regeneration after vascular injury.
Date:
2017-04
Relation:
The FASEB Journal. 2017 Apr;31(1, Suppl.):Meeting Abstract 689.19.
