The role of the Na/K-ATPase (NKA) in heart failure associated with myocardial infarction (MI) is poorly understood. The elucidation of its precise function is hampered by the existence of two catalytic NKA isoforms (NKA-α1 and NKA-α2). Our aim was to analyze the effects of an increased NKA-α2 expression on functional deterioration and remodeling during long-term MI treatment in mice and its impact on Ca handling and inotropy of the failing heart. Wild-type (WT) and NKA-α2 transgenic (TG) mice (TG-α2) with a cardiac-specific overexpression of NKA-α2 were subjected to MI injury for 8 wk. As examined by echocardiography, gravimetry, and histology, TG-α2 mice were protected from functional deterioration and adverse cardiac remodeling. Contractility and Ca transients (Fura 2-AM) in cardiomyocytes from MI-treated TG-α2 animals showed reduced Ca amplitudes during pacing or after caffeine application. Ca efflux in cardiomyocytes from TG-α2 mice was accelerated and diastolic Ca levels were decreased. Based on these alterations, sarcomeres exhibited an enhanced sensitization and thus increased contractility. After the acute stimulation with the β-adrenergic agonist isoproterenol (ISO), cardiomyocytes from MI-treated TG-α2 mice responded with increased sarcomere shortenings and Ca peak amplitudes. This positive inotropic response was absent in cardiomyocytes from WT-MI animals. Cardiomyocytes with NKA-α2 as predominant isoform minimize Ca cycling but respond to β-adrenergic stimulation more efficiently during chronic cardiac stress. These mechanisms might improve the β-adrenergic reserve and contribute to functional preservation in heart failure. Reduced systolic and diastolic calcium levels in cardiomyocytes from NKA-α2 transgenic mice minimize the desensitization of the β-adrenergic signaling system. These effects result in an improved β-adrenergic reserve and prevent functional deterioration and cardiac remodeling.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1152/ajpheart.00808.2020 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Novel continuous and quantitative intraoperative facial nerve-monitoring system for temporal bone lesions.
Eur Arch Otorhinolaryngol
January 2025
Department of Otorhinolaryngology-Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Objective: Intraoperative systems for monitoring facial nerve function, in which temporal electrical stimulation is applied to the facial nerve through electrodes, are used in many surgeries requiring facial nerve preservation; however, continuous stimulation or quantitative evaluation of facial nerve function is difficult with this approach. We examined the usefulness of a continuous and quantitative facial nerve-monitoring system for temporal bone lesions by using our experience to modify the existing methods used for cases involving vestibular schwannomas.
Study Design: Retrospective observational study.
Effects of thread design on soft and hard tissue healing around implants in lipopolysaccharide-induced peri-implantitis-like lesions in rat maxillae.
J Oral Biosci
January 2025
Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8588, Japan. Electronic address:
Objectives: This study investigated the effects of thread design on the soft and hard tissues around implants in rat maxillary peri-implantitis-like lesions.
Methods: Fourteen, 9-week-old, female Wistar rats were used in this study. Two types of grade IV titanium tissue-level implants with a standard V-shape and buttress threads were prepared (control and test implants, respectively).
Clinical Observation of VR Virtual Reality Rehabilitation Training Combined with Acupuncture in the Treatment of Mild Cognitive Impairment.
SLAS Technol
January 2025
Faculty of Medicine, Jingchu Institute of Technology, Jingmen 448000, Hubei, China. Electronic address:
Mild cognitive impairment (MCI) is an intermediate state between normal aging and dementia, and its symptoms include easy forgetting, distraction, and mental deterioration. This directly affects the patient's motor function, daily living ability, and social adaptability, and brings many difficulties to the patient's reintegration into society. Therefore, clinical research on MCI is very necessary.
View Article and Find Full Text PDFPiplartine alleviates sepsis-induced acute kidney injury by inhibiting TSPO-mediated macrophage pyroptosis.
Biochim Biophys Acta Mol Basis Dis
January 2025
Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. Electronic address:
Sepsis-induced acute kidney injury (SI-AKI) is the most common organ dysfunction of sepsis, characterized with prolonged hospitalization periods and significantly elevated mortality rates. Piplartine (PLG), an alkaloid extracted from Piper longum within the Piperaceae family, has exhibited diverse pharmacological activities, including anti-inflammatory, anti-atherosclerotic, and anti-tumor effects. Herein, we investigated whether the PLG could reverse SI-AKI and explore its possible anti-inflammatory mechanisms.
View Article and Find Full Text PDFMechanically robust, mouldable, dynamically crosslinked hydrogel flap with multiple functionalities for accelerated deep skin wound healing.
Biomater Adv
January 2025
Department of Biological Sciences and Engineering, Indian Institute of Technology Gandhinagar, Gujarat, India. Electronic address:
Deep cutaneous wounds, which are difficult to heal and specifically occur on dynamic body surfaces, remain a substantial healthcare challenge in clinical practice because of multiple underlying factors, including excessive reactive oxygen species, potential bacterial infection, and extensive degradation of the extracellular matrix (ECM) which further leads to the progressive deterioration of the wound microenvironment. Any available individual wound therapy, such as antibiotic-loaded cotton gauze, cannot address all these issues. Engineering an advanced multifunctional wound dressing is the current need to promote the overall healing process of such wounds.
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!