Ceramide-coated balloon catheters limit neointimal hyperplasia after stretch injury in carotid arteries

Neointimal hyperplasia at the site of surgical intervention is a common and deleterious complication of surgery far cardiovascular diseases. We hypoth esized that direct delivery of a cell-permeable growth-arresting lipid via the balloon tip of an embolectomy catheter would limit neointimal hyperplas ia after stretch injury. We have previously demonstrated that sphingolipid- derived ceramide arrested the growth of smooth muscle cell pericytes in vit ro, Here, we show that ceramide-coated balloon catheters significantly redu ced neointimal hyperplasia induced by balloon angioplasty in rabbit carotid arteries in vivo. This ceramide treatment decreased the number of vascular smooth muscle cells entering the cell cycle without inducing apoptosis. In situ autoradiographic studies demonstrated that inflating the balloon cath eter forced cell-permeable ceramide into the intimal and medial layers of t he artery, Intercalation of ceramide into vascular smooth muscle cells corr elated with rapid inhibition of trauma-associated phosphorylation of extrac ellular signal-regulated kinase and protein kinase B. These studies demonst rate the utility of cell-permeable ceramide as a novel therapy for reducing neointimal hyperplasia after balloon angioplasty.