The mechanisms underlying chronic kidney disease (CKD)-associated higher risks for life-threatening ventricular tachyarrhythmias remain poorly understood. In rats subjected to unilateral nephrectomy (UNx), we examined cardiac electrophysiological remodeling and relevant mechanisms predisposing to ventricular arrhythmias. Adult male Sprague-Dawley rats underwent UNx (n = 6) or sham (n = 6) operations. Eight weeks later, the UNx group had higher serum blood urea nitrogen and creatinine levels and a longer electrocardiographic QTc interval than did the sham group. Patch-clamp studies revealed epicardial (EPI)-predominant prolongation of the action potential duration (APD) at 50% and 90% repolarization in UNx EPI cardiomyocytes compared to sham EPI cardiomyocytes. A significant reduction of the transient outward potassium current (I) in EPI but not in endocardial (ENDO) cardiomyocytes of UNx rats led to a decreased transmural gradient of I. The reduction of I currents in UNx EPI cardiomyocytes was secondary to downregulation of KChIP2 but not Kv4.2, Kv4.3, and Kv1.4 protein expression. Incubation of plasma electronegative low-density lipoprotein (LDL) from UNx rats with normal EPI and ENDO cardiomyocytes recapitulated the electrophysiological phenotype of UNx rats. In conclusion, CKD disrupts the physiological transmural gradient of I via downregulation of KChIP2 proteins in the EPI region, which may promote susceptibility to ventricular tachyarrhythmias. Electronegative LDL may underlie downregulation of KChIP2 in CKD.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5240592 | PMC |
| http://dx.doi.org/10.1038/srep40676 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Protective Role of (-)-Epicatechin on Trimethylamine-N-Oxide (TMAO)-Induced Cardiac Hypertrophy via SP1/SIRT1/SUMO1 Signaling Pathway.
Cardiovasc Toxicol
December 2024
Department of Cardiology, First Affiliated Hospital, Harbin Medical University, No. 23 YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China.
Article Synopsis
- (-)-Epicatechin (EPI) shows potential benefits for heart health by inhibiting TMAO-induced cardiac hypertrophy, which is linked to cardiovascular diseases.
- The study involved both mouse models and heart cells to evaluate the effects of EPI on TMAO-induced cardiac issues, measuring outcomes through plasma TMAO levels and histological heart analyses.
- Results indicated that EPI not only improved cardiac function but also countered the harmful effects of TMAO, including the regulation of various cardiac hypertrophy markers.
Epirubicin induces cardiotoxicity through disrupting ATP6V0A2-dependent lysosomal acidification and triggering ferroptosis in cardiomyocytes.
Cell Death Discov
July 2024
Department of Cardiology, the first affiliated hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, China.
Epirubicin (EPI) is effective in the treatment of malignant cancers, but its application is limited by life-threatening cardiotoxicity. Iron homeostasis disturbance has been implicated in anthracycline induced cardiotoxicity (AIC), and ferroptosis is involved in AIC which dependent upon intracellular iron. However, the role and exact mechanisms of ferroptosis in the pathogenesis of epirubicin-induced cardiotoxicity (EIC) remain elusive.
View Article and Find Full Text PDFβ-adrenergic stimulation after rewarming does not mitigate hypothermia-induced contractile dysfunction in rat cardiomyocytes.
Cryobiology
September 2024
Department of Physiology & Biomedical Engineering, Mayo Clinic Rochester, MN, USA. Electronic address:
Victims of severe accidental hypothermia are frequently treated with catecholamines to counteract the hemodynamic instability associated with hypothermia-induced cardiac contractile dysfunction. However, we previously reported that the inotropic effects of epinephrine are diminished after hypothermia and rewarming (H/R) in an intact animal model. Thus, the goal of this study was to investigate the effects of Epi treatment on excitation-contraction coupling in isolated rat cardiomyocytes after H/R.
View Article and Find Full Text PDFHigh-speed optical imaging with sCMOS pixel reassignment.
Nat Commun
May 2024
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
Fluorescence microscopy has undergone rapid advancements, offering unprecedented visualization of biological events and shedding light on the intricate mechanisms governing living organisms. However, the exploration of rapid biological dynamics still poses a significant challenge due to the limitations of current digital camera architectures and the inherent compromise between imaging speed and other capabilities. Here, we introduce sHAPR, a high-speed acquisition technique that leverages the operating principles of sCMOS cameras to capture fast cellular and subcellular processes.
View Article and Find Full Text PDFHeart-on-a-Chip Model of Epicardial-Myocardial Interaction in Ischemia Reperfusion Injury.
Adv Healthc Mater
August 2024
Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, M5S 3E5, Canada.
Epicardial cells (EPIs) form the outer layer of the heart and play an important role in development and disease. Current heart-on-a-chip platforms still do not fully mimic the native cardiac environment due to the absence of relevant cell types, such as EPIs. Here, using the Biowire II platform, engineered cardiac tissues with an epicardial outer layer and inner myocardial structure are constructed, and an image analysis approach is developed to track the EPI cell migration in a beating myocardial environment.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!