Trimetazidine ameliorates hindlimb ischaemic damage in type 2 diabetic mice

Abstract

Background: Ischaemia caused by lower extremity artery stenosis is the main cause of peripheral artery disease (PAD) in patients with diabetes. Trimetazidine (TMZ) has traditionally been used as an anti-ischaemic drug for coronary artery disease. The effect of TMZ on PAD in a diabetic animal model and the underlying molecular mechanisms remain unclear. Methods: The db/db mice were challenged with femoral artery ligation (FAL), followed by TMZ treatment for 2 weeks. Scores on hindlimb ischaemia and function were evaluated. Histological and capillary density analyses of gastrocnemius were performed. The expression of vascular endothelial growth factor (VEGF) and myogenic regulators was also confirmed by Western blotting. We also detected serum intercellular adhesion molecule 1 (ICAM-1) level through ELISA. Results: Diabetic mice exhibited limb ulceration and motor dysfunction after FAL while TMZ-treated db/db mice exhibited milder ischaemic impairment. Furthermore, decreased capillary density in the gastrocnemius muscles of ischaemic hindlimb and reduced expressions of VEGF, myogenic markers, and serum ICAM-1 could be partially reversed by TMZ treatment. Conclusion: TMZ may alleviate hindlimb ischaemic damage in db/db mice, at least partly, through enhancing angiogenesis and promoting myogenesis in ischaemia region.Key messages TMZ intervention could alleviate hindlimb ischaemic damage in db/db mice. TMZ intervention could enhance angiogenesis and stimulate myogenesis in ischaemia region.