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Abstract. Desmoplakin (DSP), encoded by the DSP gene, is the main desmosome component and is abundant in the myocardial tissue. There are three DSP isoforms that assume the role of supporting structural stability through intercellular adhesion. It has been found that DSP regulates the transcription of adipogenic and fibrogenic genes, and maintains appropriate electrical conductivity by regulating gap junctions and ion channels. DSP is essential for normal myocardial development and the maintenance of its structural functions. Studies have suggested that DSP gene mutations are associated with a variety of hereditary cardiomyopathy, such as arrhythmia cardiomyopathy, dilated cardiomyopathy (DCM), left ventricular noncompaction, and is also closely associated with the Carvajal syndrome, Naxos disease, and erythro-keratodermia-cardiomyopathy syndrome with skin and heart damage. The structure and function of DSP, as well as the clinical manifestations of DSP-related cardiomyopathy were reviewed in this article.

Abstract. Objective:. Physiologic cardiac pacing is a novel technique which has been largely popularized in recent decades. His bundle pacing (HBP) has been long considered the most physiologic pacing method; however, with the widespread implementation of this method, its disadvantages have become apparent. In this context, left bundle branch pacing (LBBP)—directly engaged in the His-Purkinje system—has been foreseen as the best pacing method to mimic physiologic activation patterns. This review aimed to summarize recent approaches to physiologic cardiac pacing. Data sources:. This review included fully peer reviewed publications up to July 2018, found in the PubMed database using the keywords “His bundle branch pacing,” “right ventricular pacing,” and “physiologic pacing.” Study selection:. All selected articles were in English, with no restriction on study design. Results:. The HBP has been studied worldwide, and is currently considered the most physiologic pacing method. However, it has disadvantages, such as high pacing threshold, unsatisfactory sensing and long procedure times, among others. Although LBBP is theoretically superior to HBP, the clinical relevance of this difference remains under debate, as few large randomized clinical trials with LBBP have been published. Conclusions:. Although HBP indeed appears to be the most physiologic pacing method, it has certain shortcomings, such as high pacing threshold, difficult implantation due to specific anatomic features, and others. Further studies are required to clarify the clinical significance of LBBP.

Background/aim: Patients with atrial fibrillation (AF) and coronary stenting had a poor prognosis. This study aimed to assess the accuracy of CHA2DS2-VASc score for predicting and grading adverse clinical outcomes in this population. Materials and methods: We reviewed the clinical data of all patients with previously documented nonvalvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. The study population was divided into three groups: 1) Low CHA2DS2-VASc score, ≤ 2 points, 2) Intermediate score, 3-4 points, and 3) High score, ≥ 5 points. Major adverse cardiac/cerebrovascular events (MACCE) were defined as a composite of all-cause death, nonfatal myocardial infarction, repeat revascularization and ischemic stroke/systemic thromboembolism (IS/SE). Results: A total of 2394 patients (men: 72.3% vs. women: 27.7%, median age: 67 years) were included, with the CHA2DS2-VASc score of 3.6 ± 1.6. The median follow-up duration was 36.2 months. All-cause mortality increased 3 folds from the low score (4.8%) to the high score group (15.8%). The high score group had more IS/SE (7.4%) and MACCE (26.3%). The CHA2DS2-VASc score ≥ 5 points was independently associated with all-cause death (hazard ratio [HR]: 2.303, 95% confidence interval [CI]: 1.492-3.555), IS/SE (HR: 4.169, 95% CI: 2.216-7.845) and MACCE (HR: 1.468, 95% CI: 1.113-1.936) on multivariate Cox proportional hazards regression. The area under the receiver operating characteristic curve of the CHA2DS2-VASc score was 0.644 (95% CI: 0.624-0.663) for all-cause death, 0.647 (95% CI: 0.627-0.666) for IS/SE, and 0.592 (95% CI: 0.572-0.611) for MACCE. Conclusion: CHA2DS2-VASc score was a reliable prognostic indicator in patients with AF and coronary stenting. [ABSTRACT FROM AUTHOR]

Background: The long-term mortality, thrombotic risk and bleeding complications of very old patients (≥ 80 years) with atrial fibrillation (AF) and coronary stenting were less studied. Methods: We enrolled 1504 patients ≥ 65 years with nonvalvular AF undergoing coronary stenting between January 2010 and June 2015 from 12 hospitals in Beijing, China. Results: 164 patients (10.9%) had ages ≥ 80 years. Very old patients had higher prevalence of cardiac dysfunction, renal dysfunction (RD, creatinine clearance < 60 ml/min), anemia and acute ST segment elevation myocardial infarction (STEMI) than younger patients. The mean follow-up duration was 39.0 ± 18.7 months. Complete follow-up data was obtained for 94.3% of the whole cohort. Very old patients had higher mortality (22.8% vs. 10.6%, p < 0.001), more major adverse cardiac/cerebrovascular events (MACCE, 33.6% vs. 18.5%, p < 0.001), and major bleeding events (MB) (5.4% vs. 2.8%, p = 0.150) than younger controls. For very old patients, multivariate Cox regression identified cardiac dysfunction (HR: 2.564, 95% CI: 1.279-5.139, p = 0.008), RD (HR: 4.001, 95% CI: 1.518-10.546, p = 0.005) and STEMI (HR: 2.529, 95% CI: 1.275-5.013, p = 0.008) as independent predictors for all-cause death; cardiac dysfunction (HR: 2.590, 95% CI: 1.470-4.565, p = 0.001) and RD (HR: 4.204, 95% CI: 1.865-9.476, p = 0.001) as independent predictors for MACCE; cardiac dysfunction (HR: 2.417, 95% CI: 1.399-4.176, p = 0.002), RD (HR: 4.278, 95% CI: 1.997-9.164, p < 0.001) and STEMI (HR: 1.767, 95% CI: 1.008-3.097, p = 0.047) as independent predictors for the composite endpoint ofMACCE and MB. Conclusion: Very old patients with AF and coronary stenting had a poor long-term prognosis, with cardiac dysfunction and RD as independent risk factors. [ABSTRACT FROM AUTHOR]

The endoplasmic reticulum (ER) is an organelle in which proteins form their appropriate structures. However, several of these proteins become unfolded or misfolded when exposed to stimuli, including hyperglycemia, oxidative stress, ischemia, disturbance of calcium homeostasis and overexpression of abnormal proteins, which activates ER stress and the unfolded protein response (UPR). To date, investigations have demonstrated that ER stress is important in diabetic myocardial fibrosis by inducing cardiac cell apoptosis. Therefore, in the present study, the polymerase chain reaction, western blotting analysis and tissue staining were performed to identify the changes in UPR signaling proteins and apoptotic proteins in diabetic rats at different time points, and to determine whether the myocardial fibrosis is associated with ER-stress-mediated apoptosis using a diabetes mellitus (DM) rat model. It was found that the upregulation of ER stress markers and apoptotic molecules developed over time. It was also demonstrated that anti-apoptotic markers and proapoptotic markers were activated early following model establishment, and then decreased in months 4 and 5. The changes in myocardial fibrosis were found to accelerate in a time-dependent manner with apoptosis in the DM rats. [ABSTRACT FROM AUTHOR]

Background Cardiac dysfunction in diabetic cardiomyopathy may be associated with abnormal Ca2+ homeostasis. This study investigated the effects of alterations in Ca2+ homeostasis and sarcoplasmic reticulum Ca2+-associated proteins on cardiac function in the development of diabetic cardiomyopathy. Methods Sprague-Dawley rats were divided into 4 groups (n = 12, each): a control group, and streptozotocin-induced rat models of diabetes groups, examined after 4, 8, or 12 weeks. Evaluations on cardiac structure and function were performed by echocardiography and hemodynamic examinations, respectively. Cardiomyocytes were isolated and spontaneous Ca2+ spark images were formed by introducing fluorescent dye Fluo-4 and obtained with confocal scanning microscopy. Expressions of Ca2+-associated proteins were assessed by Western blotting. Results Echocardiography and hemodynamic measurements revealed that cardiac dysfunction is associated with the progression of diabetes, which also correlated with a gradual but significant decline in Ca2+ spark frequency (in the 4-, 8- and 12-week diabetic groups). However, Ca2+ spark decay time constants increased significantly, relative to the control group. Expressions of ryanodine receptor 2 (RyR2), sarcoplasmic reticulum Ca2+-2ATPase (SERCA) and Na +/Ca 2+ exchanger (NCX1) were decreased, together with quantitative alterations in Ca2+regulatory proteins, FKBP12.6 and phospholamban progressively and respectively in the diabetic rats. Conclusions Ca2+ sparks exhibited a time-dependent decay with progression of diabetic cardiomyopathy, which may partly contribute to cardiac dysfunction. This abnormality may be attributable to alterations in the expressions of some Ca2+-associated proteins. [ABSTRACT FROM AUTHOR]

A new heterobimetallic ruthenium(II)-rhenium(I) complex of [Ru(bpy)2(HL)Re(CO)2Cl](ClO4)2.6H2O (RuHLRe) {bpy = 2,2'-bipyridine and HL = 2-(4-(2,6-di(pyridin-2-yl)pyridin-4-yl)phenyl)-1H-imidazo[4,5-f]- [1,10]phenanthroline} was synthesised and characterised by elemental analysis, proton nuclear magnetic resonance spectroscopy, and mass spectrometry. The ground- and excited-state acid-base properties of RuHLRe were studied using UV-Vis absorption spectrophotometric and spectrofluorimetric titrations in a 100 : 1 (v/v) Britton-Robinson buffer-CH3CN solution combined with luminescence lifetime measurements. The complex exhibited two-step separate protonation-deprotonation processes in both the ground and excited states. The complex acted as pH-induced "off-on-off" luminescence switches (Ion/ Ioff = 31.0 and 14.6), with one of the switching actions being driven by pH variations over the physiological pH range (5.3-8.0). Importantly, cellular imaging and cytotoxicity experiments demonstrated that RuHLRe rapidly and selectively illuminated the membrane of HeLa cells over fixed cells and exhibited reduced cytotoxicity at the imaging concentration compared to the Re(I)-free parent Ru(II) complex. In addition, RuHLRe acted as an efficient "turn on" emission sensor for H2PO4 - and "turn off" emission sensor for F- and OAc-. [ABSTRACT FROM AUTHOR]