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Proprotein convertase subtilisin/kexin (PCSK) family member 3 (FURIN) has been suggested to be involved in the development of atherosclerosis. The aim of this study was to investigate the prognostic implication of FURIN in patients after acute myocardial infarction (AMI).This prospective study analyzed data from a total of 1312 consecutive patients hospitalized with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction from August 2013 to June 2016. FURIN levels were analyzed in plasma obtained from AMI patients.The study included 1312 AMI patients. The patient population was predominantly male (63%) with a median age of 66 years (IQR: 19 years), and 59% were STEMI patients. During a follow-up of 2 years, 117 patients died, and 377 patients reached the combined endpoints of major adverse cardiac events (MACE). Patients with elevated FURIN levels had increased risk of MACE, all-cause mortality, recurrent MI and hospitalization for HF (log-rank test, p 0.0001). After adjusting for clinical risk factors and established markers, the association of FURIN concentrations with the risk of MACE and its individual components and cardiovascular death was statistically significant in the higher tertile of FURIN concentrations. After the addition of FURIN to the models, FURIN showed additive prognostic significance for 2-year clinical outcomes. Variable importance plots of the models showed that FURIN was of high importance to predict both occurrence of MACE and all-cause mortality.We found that FURIN was associated with all-cause mortality and recurrent cardiovascular events in AMI patients independent of conventional risk factors and established markers.

Background/Aims: To explore the potential role of qiliqiangxin (QLQX) A traditional Chinese medicine and the involvement of angiotensin II receptor type 1 (AGTR1) and transient receptor potential vanilloid 1 (TRPV1) in diabetic mouse cardiac function. Methods: Intragastric QLQX was administered for 5 weeks after streptozotocin (STZ) treatment. Additionally, Intraperitoneal injections of angiotensin II (Ang II) or intragastric losartan (Los) were administered to assess the activities of AGTR1 and TRPV1. Two-dimensional echocardiography and tissue histopathology were used to assess cardiac function Western blot was used to detect the autophagic biomarkers Such as light chain 3 P62 and lysosomal-associated membrane protein 2 And transmission electron microscopy was used to count the number of autophagosomes. Results: Decreased expression of TRPV1 and autophagic hallmarks and reduced numbers of autophagolysosomes as well as increased expression of angiotensin converting enzyme 1 and AGTR1 were observed in diabetic hearts. Blocking AGTR1 with Los mimicked the QLQX-mediated improvements in cardiac function Alleviated myocardial fibrosis and enabled autophagy Whereas Ang II abolished the beneficial effects of QLQX in wild type diabetic mice but not in TRPV1-/- diabetic mice. Conclusions: QLQX may improve diabetic cardiac function by regulating AGTR1/ TRPV1-mediated autophagy in STZ-induced diabetic mice.

Limited published data about periprocedural myocardial injury (PMI) after successful chronic total occlusion (CTO)-percutaneous coronary intervention (PCI) were available. The study aimed to investigate risk predictors and clinical implications of PMI after successful CTO-PCI and drug-eluting stent (DES) implantation. Between 2009and 2012, a total of 437 patients who underwent successful recanalization with DESs were included. All the cardiac troponin T (cTnT)-positive patients were excluded. As the benchmark in PMI defined as cTnT >5 × the 99th percentile ULN, the independent predictors and major adverse cardiac events (MACEs) involving cardiac death, myocardial infarction, and target-vessel revascularization were compared between the PMI group and the no PMI group. The incidence rate of PMI was 18.3% (80/437) after the index procedure. Multivariate analysis showed that calcification (OR: 2.203, confidence interval [CI] 1.262–3.845, P = 0.005), the parallel wire technique (OR: 3.178, CI 1.661–6.081, P < 0.001), and the retrograde wire technique (OR: 5.554, CI 2.275–13.558, P < 0.001) were independent predictors of PMI after successful CTO-PCI and DES implantation. Major adverse cardiac events were significantly higher in the PMI group (adjusted hazard ratio 3.704; 95% CI 1.759–7.796; P = 0.001) during the 3-year follow-up. The independent predictors of PMI after successful recanalization with DESs are calcification, the parallel wire technique, and the retrograde wire technique. Periprocedural myocardial injury after the index procedure is associated with more adverse clinical events. Further large clinical studies combined with bioinformatics are warranted to explore the implications of patients with this distinct new entity.

Objective The study aimed to analyze the risk factors and long-term outcomes associated with coronary artery aneurysms (CAAs) after successful percutaneous coronary intervention (PCI) and drug-eluting stent (DES) implantation in patients with CTOs. Background There are sporadic data available on post-procedure CAAs after transcatheter revascularization for CTOs. Methods and results A total of 141 patients with 149 CTOs who underwent successful CTO-PCI and DES implantation with angiographic follow-up from 2004 to 2010 were included. Patients were divided into CAA group and non-CAA group according to the presence of CAAs in the follow-up angiography. The independent predictors and major adverse cardiac events (MACEs) including cardiac death, myocardial infarction (MI) and target-vessel revascularization (TVR) were compared between two groups. The incidence of CAAs was 11.4% (17/149) after index procedure. Multivariate analysis showed that age (OR: 0.925, CI 0.873–0.980, P = 0.008), ostial occlusion (OR: 6.715, CI 1.473–30.610, P = 0.014), the parallel wire technique (OR: 6.167, CI 1.709–22.259, P = 0.005) and DES length (OR: 1.030, CI 1.002–1.058, P = 0.036) were the independent predictors of CAAs after successful CTO-PCI and DES implantation. MACEs were similar between two groups (adjusted hazard ratio 0.670; 95% CI 0.160–2.808; P = 0.584) during the 5-year follow-up. Conclusions The independent predictors of CAAs after successful CTO-PCI and DES implantation are age, ostial occlusion, the parallel wire technique and DES length. CAAs after index procedure are not frequently associated with adverse clinical events under dual antiplatelet therapy. Further large clinical studies are warranted to explore the clinical implications of patients with this distinct new entity.

Objectives The aim of this study was to investigate the effectiveness and safety of aggressive statin versus moderate statin therapy on patients with saphenous vein grafts (SVGs) in randomized, controlled trials (RCTs). Methods We searched MEDLINE (1980–June 2012), the Cochrane Controlled Trials Register, EMBASE, Science Citation Index, and PubMed (to June 2012), and found 10 relevant RCTs, including 7 substudy analyses from a Post-CABG trial, and 1 pooled analysis of the PROVE-IT TIMI 22 trial (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators) and A to Z trial. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes; phase Z of the A to Z trial. Results A total of 6645 of participants, ages ranging from 21 to 75 years old, were treated with coronary artery bypass graft (CABG) and were followed for 2 to 5 years. Eight studies showed that aggressive statin therapy had lower LDL-C levels and a decrease of 39% in graft atherosclerotic progression, 12% in new occlusions, and 19% in new lesions more than moderate statin therapy. Three reports indicated that aggressive statin therapy lowered the risk of repeated myocardial infarction more than moderate statin therapy for coronary revascularization (95% CI, 0.66–0.95; risk ratio [RR] = 0.80; and 95% CI, 0.66–0.85; RR = 0.75) and lowered the risk of cardiac death as well (95% CI, 0.64–1.08; RR = 0.83). Aggressive statin therapy had safety similar to that of moderate statin therapy except for a slight increase in myopathic events and aminotransferase levels. Seventy percent to 90% of patients took statin treatment as prescribed in long-term. Conclusions Compared with moderate statin therapy, long-term aggressive statin lowered the LDL-C level significantly, further decreased the atherosclerotic progression of SVG, reduced the risks of repeated myocardial infarction and coronary revascularization after CABG, and revealed similar patient compliance and statin-related adverse effects but slightly increased myopathy events and aminotransferase levels.

Endothelial dysfunction and oxLDL are believed to be early and critical events in atherogenesis. 6-Shogaol is the major bioactive compound present inZingiber officinaleand possesses the anti-atherosclerotic effect. However, the mechanisms remain poorly understood. The goal of this study was to investigate the effects of 6-shogaol on oxLDL-induced Human umbilical vein endothelial cells (HUVECs) injuries and its possible molecular mechanisms. Hence, we studied the effects of 6-shogaol on cell apoptosis, cellular reactive oxygen species (ROS), NF-κB activation, Bcl-2 expression, and caspase -3, -8, -9 activities. In addition, E-selectin, MCP-1, and ICAM-1 were determined by ELISA. Our study show that oxLDL increased LOX-1 expression, ROS levels, NF-κB, caspases-9 and -3 activation and decreased Bcl-2 expression in HUVECs. These alterations were attenuated by 6-shogaol. Cotreatment with 6-shogaol and siRNA of LOX-1 synergistically reduced oxLDL-induced caspases -9, -3 activities and cell apoptosis. Overexpression of LOX-1 attenuated the protection by 6-shogaol and suppressed the effects of 6-shogaol on oxLDL-induced oxidative stress. In addition, oxLDL enhanced the activation of NF-κB and expression of adhesion molecules. Pretreatment with 6-shogaol, however, exerted significant cytoprotective effects in all events. Our data indicate that 6-shogaol might be a potential natural antiapoptotic agent for the treatment of atherosclerosis.

Aortic valve calcification (AVC) is common in the elderly and associated with increased cardiovascular mortality, while diabetes is one of the confirmed risk factors for coronary artery disease (CAD). In this study, we aimed to evaluate the prevalence and severity of CAD in type-2 diabetic patients with AVC.From June to December in 2007, a total of 325 consecutive patients with chest pain or chest distress were admitted for coronary angiography. The severity of CAD was evaluated by the Gensini score and the number of stenosed vessels. All patients underwent transthoracic echocardiography for detecting AVC.Compared with the patients without diabetes (n = 221), the type-2 diabetic patients (n = 104) had a similar prevalence of CAD (66.5% vs. 72.1%, P = 0.312). Further classified by the presence of AVC, patients with AVC had a higher prevalence of CAD, average Gensini score and the number of stenosed vessels, both in the group with and without diabetes. It was also demonstrated that the odds ratio (OR) of AVC for CAD in the diabetic patients was higher than in the non-diabetic ones (3.405 vs 2.515) after chi-square analysis (single-variable). However, at multivariable logistic regression analysis for CAD, the OR of AVC was 3.757 (P = 0.03) in diabetic group, while it did not achieve statistical significance in the non-diabetic group (OR = 2.130, P= 0.074).Type-2 diabetic patients with AVC had a higher prevalence of and more severe CAD.

Background: Although the sirolimus-eluting stent (CYPHER®, Cordis, USA) has shown a dramatic reduction of restenosis, there are still some concerns about its efficacy and safety. Its durable polymer coating may enhance neointimal proliferation and residual sirolimus, which cannot be released from polymer, may result in incomplete reendothelization. As a drug reservoir, bioabsorbable polymer (polylactic acid, PLA) is more rational. Objective: We aimed to determine the safety and efficacy of sirolimus-eluting stent coated with PLA (EXCEL®, JW Medical Systems, China) in the treatment of human coronary arterial diseases. Methods: The study included 31 patients with de novo coronary lesions, with vessels 2.5–3.5 mm in diameter. The primary end points included the percentage of in-stent restenosis of the luminal diameter and in-stent late luminal loss at 6 months, as determined by quantitative angiography. The secondary end point was the major adverse cardiac events (MACE) 30 days and 6 months after the index procedure. Results: Forty-eight EXCEL stents were successfully delivered in the 34 lesions, and multiple stents were implanted in 35.3% of lesions. All patients were discharged without clinical complications and completed clinical follow-up at 1 and 6 months. No MACE had occurred. Twenty patients (30 stents) completed 6 months of angiographic follow-up. No in-stent or in-lesion restenosis (diameter stenosis ≥≥50%) was observed. In-stent late loss was (0.07 ± 0.17) mm. Conclusions: The implantation of EXCEL stent is feasible and safe and elicits minimal neointimal proliferation. This new stent has potential advantages regarding the long-long-term result over the commercially stent as the new stent has no sustained stimulation to the local tissue. © 2006 Wiley-Liss, Inc.

Objective: In-stent restenosis is caused by the neointimal hyperplasia, which involves abnormal growth of vascular smooth muscle cells (VSMC). Arsenic trioxide (As2O3) is known to be a potent inhibitor of cell proliferation. We therefore studied the role of an As2O3 eluting stent in the prevention of restenosis in a rabbit iliac artery model. Methods and results: Bare stents, or stents coated with poly-l-lactic acid (PLLA) and either 40 μg of As2O3, 180 μg of paclitaxel or vehicle were implanted into the left proximal iliac arteries of New Zealand rabbits. The delivery of drugs from stents in vitro and in vivo was evaluated by atomic fluorescence spectrophotometry and high-performance liquid chromatography, respectively. Histomorphometric measurements at 7 or 28 days showed that, comparing to rabbits receiving the PLLA stent, in animals treated with As2O3 eluting or paclitaxel eluting stent neointima thickness was reduced by 50% and 46%, the absolute neointimal area was reduced by 53% and 44%, while the absolute luminal area was increased by 46% and 43%, respectively. There were no significant differences in injury or inflammation scores among PLLA, As2O3 eluting and paclitaxel eluting stents. As2O3 eluting stent induced more TUNEL-positive VSMC than the other stents. As2O3 levels measured in the arterial tissue were much higher than those in serum, which were nearly undetectable at 7 days after stent implantation. In in vitro studies, cultured rabbit arterial VSMC were stimulated with As2O3 or paclitaxel and analyzed for their cell cycle progression and apoptosis by flow cytometry and electron microscopy. As2O3 treatment resulted in a reduction of VSMC number in G1 phase with a concomitant increase in apoptosis of VSMC, whereas paclitaxel treatment led to blocking of VSMC in the G2/M phase. Conclusion: In a rabbit iliac artery model PLLA coated As2O3 eluting stent significantly suppressed in-stent restenosis by reducing proliferation and inducing apoptosis of VSMC.

Aims We sought to determine whether repeat administration of bone marrow mononuclear cells (BMC) can improve left ventricular function compared with a single infusion in patients with large acute myocardial infarction (AMI). Methods and results Thirty-nine patients with a ST-elevation AMI of the anterior wall and a significantly decreased left ventricular ejection fraction (LVEF 20–39%) were randomly assigned to three groups following primary percutaneous coronary intervention: Group A (n = 12) received a single intracoronary infusion of BMC (1.9 ± 1.2 × 108) at 3–7 days after AMI; Group B (n = 15) received BMC administration both at 3–7 days (2.0 ± 1.4 × 108) and at 3 months (2.1 ± 1.7 × 108); and the control group (CON, n = 12) received one placebo injection at 3–7 days. We noted no severe complications associated with the BMC transfer. The increase in LVEF evaluated by magnetic resonance imaging (MRI) after 12 months in Group B (11.7 ± 2.6%) was significantly greater than that in Group A (7.2 ± 1.6%, P < 0.001) or in CON (2.9 ± 2.0%, P < 0.001). Magnetic resonance imaging-derived myocardial infarct size decreased significantly in Group B compared with Group A (11.3 ± 2.7% vs. 6.3 ± 1.6%, P < 0.001). Conclusion Data from this preliminary study suggest that repeated BMC administration might be a safe and feasible therapeutic strategy for patients with large AMI.

Recently, the use of sirolimus-eluting stents (SES) has been demonstrated to significantly reduce the rate of adverse events among selected patients with ST-segment elevation acute myocardial infarction (STEMI). We present real-world experience from a single center registry evaluating the safety and efficacy of primary percutaneous coronary intervention (PCI) in unselected patients with STEMI using SES. Clinical outcome at 300-day follow-up in two cohorts of 225 consecutive patients who underwent bare metal stent (BMS) (January 2004 - February 2005, n = 123) or SES (March 2005 - December 2006, n = 102) implantation was examined. The primary endpoint was a composite of major adverse cardiovascular events (MACE: death, nonfatal reinfarction, and target vessel revascularization [TVR]). The incidence of short-term MACE was similar between the SES group and BMS group (30-day rate of MACE: 4.9% versus 8.9%, P = 0.30). Angiographically documented stent thrombosis within 30 days after primary PCI was not diagnosed in any patient in the SES group and occurred in 1 patient treated with BMS (0 versus 0.8%, P = 1.0). At 300 days, SES implantation significantly reduced the incidence of MACE (7.8% versus 22.8%, hazard ratio [HR] 0.32 [95% confidence interval (CI) 0.15 to 0.71], P = 0.005), mainly due to a marked reduction in the risk of TVR (1.0% versus 17.1%, HR 0.05 [95% CI 0.01 to 0.39], P < 0.001). There was no new onset of documented stent thrombosis between 30 and 300 days in either group. Thus, this real-world registry confirmed the safety and efficacy of SES with remarkably lower rates of TVR and MACE in the setting of primary PCI for unselected patients with STEMI in a real-world scenario.