lignans and Coronary-Restenosis

The main pathological mechanism of restenosis after percutaneous coronary intervention (PCI) is intimal hyperplasia, which is mainly caused by proliferation and migration of vascular smooth muscle cells (VSMCs). Our previous study found that honokiol (HNK), a small-molecule polyphenol, can inhibit neointimal hyperplasia after balloon injury, but its specific mechanism is still unclear. Moreover, poor water solubility as well as low bioavailability of honokiol has limited its practical use.. We used mesoporous silica nanoparticles (MSNPs) as a standard substance to encapsulate HNK and then assemble into honokiol-mesoporous silica nanoparticles, and we investigated the effect of these nanoparticles on the process of restenosis after common carotid artery injury in rats.. We report a promising delivery system that loads HNK into MSNPs and finally assembles it into a nanocomposite particle. These HNK-MSNPs not merely inhibited proliferation and migration of VSMCs by reducing phosphorylation of Smad3, but also showed a higher suppression of intimal thickening than the free-honokiol-treated group in a rat model of balloon injury.. To sum up, this drug delivery system supplies a potent nano-platform for improving the biological effects of HNK and provides a promising strategy for preventing vascular restenosis.

Topics: Animals; Biphenyl Compounds; Carotid Artery Injuries; Cell Line; Cell Proliferation; Coronary Restenosis; Disease Models, Animal; Drug Delivery Systems; Humans; Lignans; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Nanoparticles; Percutaneous Coronary Intervention; Poloxamer; Rats, Sprague-Dawley; Silicon Dioxide

The pathological mechanism of percutaneous transluminal coronary angioplasty-induced restenosis has been attributed to outgrowth of vascular smooth muscle cells. Pretreatment with antioxidants has been shown to reduce restenosis. Magnolol, an active compound of Magnolia officinalis, has exhibited approximately 1,000 times more potent antioxidant effects than alpha-tocopherol. In this study, we demonstrate, using cytometric analysis, an approximate 61% reduction of smooth muscle cells progressing to the S-phase by 0.05 mg/ml of magnolol. A BrdU incorporation assay also showed a significant reduction (73%) of DNA synthesis using 0.05 mg/ml of magnolol. The protein level of the proliferating cell nuclear antigen was suppressed by approximately 48% using 0.05 mg/ml of magnolol. This was in agreement with the promoter activity of nuclear factor-kappa B, which was also attenuated by 0.05 mg/ml of magnolol. Since receptor interacting protein and caspase-3 protein expression levels were both increased by magnolol in a dose-dependent manner, the apoptotic pathway may mediate the inhibition of cell growth. Our finding that malondialdehyde formation was significantly inhibited by 0.05 mg/ml of magnolol further supported the antioxidant effect of magnolol. These studies suggest that magnolol might be a potential pharmacological reagent in preventing balloon injury-induced restenosis.

Topics: Angioplasty, Balloon, Coronary; Animals; Antioxidants; Biphenyl Compounds; Blotting, Western; Caspase 3; Caspases; Cell Cycle; Cell Proliferation; Cells, Cultured; Coronary Restenosis; DNA; Dose-Response Relationship, Drug; Lignans; Malondialdehyde; Muscle, Smooth, Vascular; NF-kappa B; Proliferating Cell Nuclear Antigen; Promoter Regions, Genetic; Protein Serine-Threonine Kinases; Rats; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins