Inhibition of mitochondrial fission as a potential therapeutic target for vascular disease?

Stents are small metal scaffold tubes, implanted into blocked coronary arteries in order to restore blood flow in patients with coronary heart disease. 1 The most advanced stents are drug-eluting stents (DES, which address the issue of vessel re-narrowing (restenosis) by inhibition of smooth muscle cell (SMC) proliferation. DES have limitations, most significantly occlusion of the vessel due to late stent thrombosis. 2 This partly arises due to inhibitory effects of the drugs on endothelial cells (EC), delaying recovery of the endothelium. 3 Recent research has identified Mdivi-1 (mitochondrial division inhibitor-1) as a potential drug candidate for preventing restenosis and other vascular diseases.4,5 This is due to Mdivi-1’s inhibitory effects on mitochondrial fission, preventing SMC proliferation. This study sought to characterise the effects of Mdivi-1 on EC function. Determinations of proliferation, migration and toxicity were carried out. Mitochondrial morphology assessment was undertaken using fluroesence microscopy. Results demonstrate a significant potential role for Mdivi-1 in the modulation of EC survival, proliferation and migration. This has important implications on Mdivi-1’s suitability as a substance within DES and as a treatment of vascular disease.