The Role of Apolipoprotein A-I in Improving Stent Biocompatibility

Abstract

While the primary success rate after a percutaneous coronary intervention (PCI) is high, stent failure as a result of neointimal hyperplasia, inadequate re-endothelialisation or in-stent thrombosis remain significant problems. High density lipoproteins (HDL) regulate a number of biological processes involved in stent biocompatibility. Therefore, it is proposed apolipoprotein (apo) A-I, HDLs main protein constituent, may be used to improve stent biocompatibility. Using the murine thoracic aorta carotid interposition grafting model apoA-I was raised systemically or locally to investigate all areas of stent biocompatibility. Systemically raising apoA-I reduced neointimal area and decreased incidence of thrombosis. There was a higher percentage of smooth muscle cell (SMC) α-actin staining, lower CD68 mRNA and increased ABCA1 and PPAR-γ mRNA expression in the arteries of mice receiving apoA-I. There was no difference in circulating leukocytes between treatment groups, however, in the injured vessel of apoA-I treated mice there were decreased macrophages and increased endothelial cells (EC). Therefore the changes in neointimal cellular phenotype are likely due to localised increases in SMC cholesterol efflux by apoA-I which positively influenced the cellular environment reducing neointima area and thrombosis. ApoA-I was delivered locally by immobilisation on a unique plasma activated coating (PAC). ApoA-I was shown to reduce thrombosis compared to stainless steel (SS) controls. ApoA-I significantly reduced SMC attachment and proliferation while increasing EC attachment on PAC samples. Additionally PAC coated stents were able to retain a monolayer apoA-I in vivo after exposure to physiological flow for three days, while the SS stents lost the majority of the protein. These studies have shown apoA-I, whether raised systemically or delivered locally, can beneficially regulate the biological processes responsible for stent failure, improving overall stent biocompatibility.