Lactic acid-mediated endothelial to mesenchymal transition through TGF-β1 contributes to in-stent stenosis in poly-L-lactic acid stent

Currently, bioresorbable stents made with biodegradable materials are attracting more and more attentions in cardiovascular tissue engineering. Especially, poly-L-lactic acid (PLLA) stent has been regarded as the most promising one due to excellent biodegradability until serious in-stent restenosis at late stage was reported. This imply that the PLLA stent has side effect in cell function, and it is rarely reported the effect of degradation product of PLLA on endothelial function. Here we reported that lactic acid (LA) not acidic pH induced endothelial-to-mesenchymal transition (EndMT) leading to vascular fibrosis which may contribute to in-stent stenosis after PLLA stent implantation. Furthermore, we found TGF-β1 signaling was involved in boosting EndMT by LA. These results demonstrate a mechanism of in-stent stenosis induced by PLLA and indicate its utility for the future design of polymeric vascular scaffolds.