Objective: Tetramethylpyrazine, a drug originally isolated from the rhizome of Ligusticum walliichi, is an inhibitor of phosphodiesterase and inhibits platelet aggregation and smooth muscle cell proliferation. The effect of the tetramethylpyrazine-eluting stent (TES) on preventing in-stent restenosis was investigated in comparison with control bare metal stents in a porcine coronary stent restenosis model. Methods: The TES was prepared by spray-coating the 2.5 to 3.0mm×15 to 20mm bare metal stents with Tetramethylpyrazine monomer, methyl methacrylate copolymer, and polyglycolic acid. Stent overdilation injury (stent:artery=1.1 to 1.2:1.0) was made with control bare stents (n=5) and TES (n=5) in porcine coronary arteries. Follow-up quantitative coronary angiography (QCA) and histopathological assessments of stented coronary arteries were performed 4 weeks after stenting. Results: Quantitative coronary angiography showed the late lumen loss (0.28±0.08mm versus 1.70±0.52mm; P=0.004) and percentage diameter stenosis (10.0±2.1% versus 60.2±23.5%; P=0.01) were significantly lower in the TES group than that in the control group. Histopathological assessments of stented coronary arteries showed that the injury score and the in-stent area were similar between the groups (P＞0.05), whereas the lumen area was significantly larger (4.34±0.93 mm2 versus 1.29±1.02mm2; P=0.011) in the TES group than that in the control group. The number of proliferating cell nuclear antigen-positive cells was also significantly decreased in the TES group compared with the control group (14.7±2.5% versus 23.6±3.2%; P=0.008). Moreover, apoptosis was enhanced in TES group while regrowth of endothelium was similar between the groups. Conclusions: TES inhibited the neointimal hyperplasia and reduced in-stent restenosis in a porcine coronary artery restenosis model.

Background Two single nucleotide polymorphisms (SNPs, rs10757278 and rs2383207) on chromosome 9p21 have been proved to be associated with myocardial infarction. We investigated whether these two genetic markers are determinants of early-onset coronary artery disease. Methods and results A total of 444 consecutive patients were studied including 212 cases with coronary stenosis C50% or previous myocardial infarction and 232 controls without documented coronary artery disease. Ligase detection reaction was performed to detect two SNPs. After adjustment of clinical parameters, significant associations were identified for the rs2383207 and rs10757278 SNPs, with A/G and G/G genetypes at rs10757278 and G/G genetype carriers at rs2383207 having a higher risk of early-onset coronary artery disease than carriers of A/A genotype (odds ratio [OR] 2.207, 95% CI: 1.069-4.394, P=0.028; OR 3.051, 95% CI: 1.086-8.567, P=0.004; OR 2.964, 95% CI: 1.063-8.265, P=0.038, respectively). There were no associations between rs10757278 and rs2383207 genotypes and the severity of coronary artery disease (both P[0.05). Conclusions The rs10757278 and rs2383207 variants are determinants for early-onset coronary artery disease. These markers may help the identification of patients at increased risk for early-onset coronary artery disease.

Background Mesenchymal stem cells (MSCs) transplantation provides a new approach for myocardial repair. However, many important fundamental questions about MSCs transplantation remain unanswered. There is an urgent need to identify MSCs from the beating heart and analyze the efficacy of this new approach. This study aimed to localize the magnetically labeled MSCs (MR-MSCs) and monitor the restorative effects of MR-MSCs with magnetic resonance (MR) imaging. Methods Acute myocardial infarction (AMI) was created in swine by a balloon occlusion of the left anterior descending coronary artery. Cells were delivered via intracoronary infusion after myocardial infarction. Infarct size change and cardiac function were assessed with 3.0T MR scanner. The results were then confirmed by histological and western blot analysis. All statistical procedures were performed with Systat (SPSS version 12.01). Results A total of 26 swine were divided into four groups (sham-operated group, n=6; AMI group with PBS transplantation, n=6; labeled MSCs group, n=7; unlabeled MSCs group, n=7). MSCs, MR-MSCs (107cells) or PBS were delivered by intracoronary injection after MI and serial cardiac MR imaging studies were performed at 0, 4 and 8 weeks after transplantation. MR imaging demonstrated MI size decreased after MSCs transplantation in labeled and unlabeled groups, however, increases were seen in the AMI group at 8 weeks after MI. The left ventricular ejection fraction (LVEF) was slightly increased in the AMI group ((41.87±2.45)% vs (39.04±2.80)%, P＞0.05), but significantly improved in the MR-MSCs group ((56.85±1.29)% vs (40.67±2.00)%, P＜0.05) and unlabeled group ((55.38±1.07)% vs (41.78±2.08)%, P＜0.05) at 8 weeks after treatment. MR-MSCs were further confirmed by Prussian blue and immunofluorescent staining. Western blot analysis demonstrated that there was an increased expression of cardiomyocyte markers such as myosin heavy chain and troponin T in the MSCs treatment groups and the ratio of matrix metalloproteinase 2 to tissue inhibitor of metalloproteinase 1 decreased in the labeled group and unlabeled group compared with the AMI group and sham-operated group. Conclusion Transplanted MR-MSCs can regenerate new myocardium and prevent remolding in an MI model at 2-month follow-up and represent a preferred method to better understand the mechanisms of stem cell therapy in future clinical studies.