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Yu Y.,Beijing University of Chinese Medicine | Sun S.,CAS Beijing Institute of Genomics | Wang S.,Beijing University of Chinese Medicine | Zhang Q.,Beijing University of Chinese Medicine | And 4 more authors.
International Journal of Molecular Sciences

Due to drug-induced potential congestive heart failure and irreversible dilated cardiomyopathies, preclinical evaluation of cardiac dysfunction is important to assess the safety of traditional or novel treatments. The embryos of Nelumbo nucifera Gaertner seeds are a homology of traditional Chinese medicine and food. In this study, we applied the real time cellular analysis (RTCA) Cardio system, which can real-time monitor the contractility of cardiomyocytes (CMs), to evaluate drug safety in rat neonatal CMs and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). This study showed detailed biomechanical CM contractility in vitro, and provided insights into the cardiac dysfunctions associated with liensinine and neferine treatment. These effects exhibited dose and time-dependent recovery. Neferine showed stronger blocking effect in rat neonatal CMs than liensinine. In addition, the effects of liensinine and neferine were further evaluated on hiPS-CMs. Our study also indicated that both liensinine and neferine can cause disruption of calcium homeostasis. For the first time, we demonstrated the potential cardiac side effects of liensinine or neferine. While the same inhibition was observed on hiPS-CMs, more importantly, this study introduced an efficient and effective approach to evaluate the cardiotoxicity of the existing and novel drug candidates. © 2016 by the authors; licensee MDPI, Basel, Switzerland. Source

Peng P.-A.,Capital Medical University | Wang L.,Capital Medical University | Ma Q.,Capital Medical University | Xin Y.,Beijing Institute of Heart Lung and Blood Vessel Disease | And 6 more authors.
Cell Biology International

Contrast-induced acute kidney injury (CI-AKI) is associated with increasing in-hospital and long-term adverse clinical outcomes in high-risk patients undergoing percutaneous coronary intervention (PCI). Contrast media (CM)-induced renal tubular cell apoptosis is reported to participate in this process by activating endoplasmic reticulum (ER) stress. An angiotensin II type 1 receptor (AT1R) antagonist can alleviate ER stress-induced renal apoptosis in streptozotocin (STZ)-induced diabetic mice and can reduce CM-induced renal apoptosis by reducing oxidative stress and reversing the enhancement of bax mRNA and the reduction of bcl-2 mRNA, but the effect of the AT1R blocker on ER stress in the pathogenesis of CI-AKI is still unknown. In this study, we explored the effect of valsartan on meglumine diatrizoate-induced human renal tubular cell apoptosis by measuring changes in ER stress-related biomarkers. The results showed that meglumine diatrizoate caused significant cell apoptosis by up-regulating the expression of ER stress markers, including glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), CCAAT/enhancer-binding protein-homologous protein (CHOP) and caspase 12, in a time- and dose-dependent manner, which could be alleviated by preincubation with valsartan. In conclusion, valsartan had a potential nephroprotective effect on meglumine diatrizoate-induced renal cell apoptosis by inhibiting ER stress. © 2015 International Federation for Cell Biology. Source

Wu X.-F.,Capital Medical University | Liu X.-H.,Capital Medical University | Dong J.-Z.,Capital Medical University | Wang L.-Y.,Beijing Institute of Heart Lung and Blood Vessel Disease | And 4 more authors.
Cardiology (Switzerland)

Background: We evaluated the relationship between pregnancy-associated plasma protein-A (PAPP-A) and coronary plaque instability as assessed by intravascular ultrasound (IVUS). Methods: We performed greyscale IVUS analysis in culprit lesions of 93 patients with unstable angina (UA) and 72 with stable angina (SA). A sandwich enzyme-linked immunosorbent assay technique was used to assay circulating PAPP-A. Results: Patients with UA had higher PAPP-A levels than those with SA 10.8 mIU/l [interquartile range (IQR) 8.3-14.4] vs. 5.4 (IQR 2.9-9.8) mIU/l, p < 0.001]. Lesions in patients with higher PAPP-A levels were associated with larger plaque burden than lesions in patients with lower PAPP-A levels. IVUS attenuated plaque, positive remodeling and plaque rupture. Thrombus and angiographic Ambrose type-II eccentric lesions or multiple irregularities were more common in patients with higher PAPP-A levels than in those with lower PAPP-A levels. They were also more common in patients with UA and higher PAPP-A levels than in patients with (1) SA and higher PAPP-A levels, (2) UA and lower PAPP-A levels or (3) SA and lower PAPP-A levels. Conclusions: Higher PAPP-A levels were associated with coronary plaque instability in vivo and unstable symptoms in patients with coronary artery disease. © 2013 S. Karger AG, Basel. Source

Wang H.,Beijing Institute of Heart Lung and Blood Vessel Disease | Xu S.,Beijing Institute of Heart Lung and Blood Vessel Disease | Sun L.,Beijing Institute of Heart Lung and Blood Vessel Disease | Pan X.,Beijing Institute of Heart Lung and Blood Vessel Disease | And 2 more authors.

Background: Familial hypercholesterolemia (FH) is an autosomal dominant disease that primarily results from mutations in the low-density lipoprotein receptor (LDLR) gene. We investigated two unrelated Chinese FH patients using gene screening and functional analysis to reveal the pathogenicity and the mechanism by which these mutations cause FH. Methods: First, the LDLR gene was sequenced in these patients. Then, mutant receptors were transfected into human embryo kidney 293(HEK-293) cells, and a confocal laser-scanning microscope was used to observe the localization of mutant proteins. Further, the expression and the internalization activity were analyzed by flow cytometry. Finally, LDLR protein expression and stability was detected by western blot. Results: Two different LDLR class 2B mutations were detected in two patients. The C201F mutation is a known mutation. However, the G615V mutation is novel. Flow cytometry showed that the expression and internalization activity of the mutant LDLRs were reduced to 73.6% and 82.6% for G615V and 33.2% and 33.5% for C201F, respectively. Conclusions: This study identified two LDLR mutations in Chinese patients with FH and analyzed the relationship between the genotype and phenotype of these patients. We found that these mutant LDLRs were defective in transport, which led to a reduction in cholesterol clearance. These results increase our understanding of the mutational spectrum of FH in the Chinese population. Copyright: © 2014 Wang et al. Source

Zhang D.,Beijing Institute of Heart Lung and Blood Vessel Disease | Lv S.,Beijing Institute of Heart Lung and Blood Vessel Disease | Song X.,Beijing Institute of Heart Lung and Blood Vessel Disease | Yuan F.,Beijing Institute of Heart Lung and Blood Vessel Disease | And 4 more authors.

Objectives The purpose of this study was to investigate whether fractional flow reserve (FFR) should be performed for patients with coronary artery disease (CAD) to guide the percutaneous coronary intervention (PCI) strategy. Background PCI is the most effective method to improve the outcomes of CAD. However, the proper usage of PCI has not been achieved in clinical practice. Methods A meta-analysis was performed on angiography-guided PCI and FFR-guided PCI strategies. Prospective and retrospective studies were included when research subjects were patients with CAD undergoing PCI. The primary endpoint was the rate of major adverse cardiac events (MACE) or major adverse cardiac and cerebrovascular events (MACCE). Secondary endpoints included death, myocardial infarction (MI), repeat revascularisation and death or MI. Results Four prospective and three retrospective studies involving 49 517 patients were included. Absolute risks of MACE/MACCE, death, MI, revascularisation and death or MI for angiography-guided PCI and FFR-guided PCI were 34.8% vs 22.5%, 15.3% vs 7.6%, 8.1% vs 4.2%, 20.4% vs 14.8%, and 21.9% vs 11.8%, respectively. The meta-analysis demonstrated that FFRguided PCI was associated with lower MACE/MACCE (OR: 1.71, 95% CI 1.31 to 2.23), death (OR: 1.64, 95% CI 1.37 to 1.96), MI (OR: 2.05, 95% CI 1.61 to 2.60), repeat revascularisation (OR: 1.25, 95% CI 1.09 to 1.44), and death or MI (OR: 1.84, 95% CI 1.58 to 2.15) than angiography-guided PCI strategy. Conclusions This meta-analysis supports current guidelines advising the FFR-guided PCI strategy for CAD. PCI should only be performed when haemodynamic significance is found. Source

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