pitavastatin and Coronary-Restenosis

Stent implantation is the primary method used to treat coronary heart disease. However, it is associated with complications such as restenosis and late thrombosis. Despite surface modification being an effective way to improve the biocompatibility of stents, the current research studies are not focused on changes in the vascular microenvironment at the implantation site. In the present study, an adaptive drug-loaded coating was constructed on the surface of vascular stent materials that can respond to oxidative stress at the site of vascular lesions. Two functional molecules, epigallocatechin gallate (EGCG) and cysteine hydrochloride, were employed to fabricate a coating on the surface of 316L stainless steel. In addition, the coating was used as a drug carrier to load pitavastatin calcium. EGCG has antioxidant activity, and pitavastatin calcium can inhibit smooth muscle cell proliferation. Therefore, EGCG and pitavastatin calcium provided a synergistic anti-inflammatory effect. Moreover, the coating was cross-linked using disulfide bonds, which accelerated the release of the drug in response to reactive oxygen species. A positive correlation was observed between the rate of drug release and the degree of oxidative stress. Collectively, this drug-loaded oxidative stress-responsive coating has been demonstrated to significantly inhibit inflammation, accelerate endothelialization, and reduce the risk of restenosis of vascular stents

Topics: Animals; Catechin; Cell Movement; Cell Proliferation; Cells, Cultured; Coated Materials, Biocompatible; Coronary Restenosis; Cystamine; Drug Liberation; Drug-Eluting Stents; Endothelial Cells; Macrophages; Male; Myocytes, Smooth Muscle; Neovascularization, Physiologic; Oxidation-Reduction; Quinolines; Rabbits; Rats, Sprague-Dawley; Reactive Oxygen Species; Stainless Steel

Neointimal hyperplasia plays a crucial role in restenosis after stenting. The severity of neointimal thickness correlates with inflammatory reactions in the injured vessel and statins can inhibit inflammation. Pitavastatin has favorable effects on plasma lipoproteins and inflammation. Thus, we hypothesized that pitavastatin might inhibit the early inflammatory response, resulting in prevention of neointimal hyperplasia in porcine coronary arteries after stenting. Pitavastatin (18 coronaries, 40 mg per day) or placebo (20 coronaries) was administered orally from 7 days before stenting until the time of euthanasia at 3 or 28 days after stenting. The coronary artery of the animals was injured with an oversized metallic coil stent. Inflammatory cell infiltration was evaluated by scanning electron microscopy and was significantly reduced in the treated vessels compared to controls. On Day 28, intravascular ultrasound analysis revealed the neointimal area was significantly less at the stent site in the pitavastatin group than in the placebo. Histopathologic assessment showed significantly decreased in neointimal area in the pitavastatin group compared to the placebo (2.16 +/- 0.13 mm(2) versus 2.88 +/- 0.25 mm(2), p = 0.029), whereas the mean injury score in the pitavastatin group was larger than in the placebo group. In conclusion, Pitavastatin inhibited neointimal hyperplasia after stenting through a reduction of inflammatory reactions.

Topics: Animals; Coronary Disease; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Female; Hypertrophy; Male; Microscopy, Electron, Scanning; Probability; Quinolines; Random Allocation; Reference Values; Sensitivity and Specificity; Stents; Swine; Tunica Intima; Ultrasonography, Interventional