Loss of T-tubules (TT), sarcolemmal invaginations of cardiomyocytes (CMs), was recently identified as a general heart failure (HF) hallmark. However, whether TT per se or the overall sarcolemma is altered during HF process is still unknown. In this study, we directly examined sarcolemmal surface topography and physical properties using Atomic Force Microscopy (AFM) in living CMs from healthy and failing mice hearts. We confirmed the presence of highly organized crests and hollows along myofilaments in isolated healthy CMs. Sarcolemma topography was tightly correlated with elasticity, with crests stiffer than hollows and related to the presence of few packed subsarcolemmal mitochondria (SSM) as evidenced by electron microscopy. Three days after myocardial infarction (MI), CMs already exhibit an overall sarcolemma disorganization with general loss of crests topography thus becoming smooth and correlating with a decreased elasticity while interfibrillar mitochondria (IFM), myofilaments alignment and TT network were unaltered. End-stage post-ischemic condition (15days post-MI) exacerbates overall sarcolemma disorganization with, in addition to general loss of crest/hollow periodicity, a significant increase of cell surface stiffness. Strikingly, electron microscopy revealed the total depletion of SSM while some IFM heaps could be visualized beneath the membrane. Accordingly, mitochondrial Ca(2+) studies showed a heterogeneous pattern between SSM and IFM in healthy CMs which disappeared in HF. In vitro, formamide-induced sarcolemmal stress on healthy CMs phenocopied post-ischemic kinetics abnormalities and revealed initial SSM death and crest/hollow disorganization followed by IFM later disarray which moved toward the cell surface and structured heaps correlating with TT loss. This study demonstrates that the loss of crest/hollow organization of CM surface in HF occurs early and precedes disruption of the TT network. It also highlights a general stiffness increased of the CM surface most likely related to atypical IFM heaps while SSM died during HF process. Overall, these results indicate that initial sarcolemmal stress leading to SSM death could underlie subsequent TT disarray and HF setting.
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http://dx.doi.org/10.1016/j.yjmcc.2014.05.006 | DOI Listing |
Nutrients
January 2025
Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy.
Obesity is closely linked to chronic low-grade inflammation and the development of cardio-metabolic comorbidities. Monocyte subsets, which are crucial in immune responses, have been reported to be altered in individuals with obesity, potentially exacerbating inflammation. Although very-low-calorie ketogenic diets (VLCKDs) are recognized for their efficacy in promoting weight loss and improving metabolic health, their impact on circulating monocyte subsets remains poorly understood.
View Article and Find Full Text PDFStem Cell Reports
January 2025
Toronto General Hospital Research Institute, University Health Network, 101 College St., Toronto, ON M5G 1L7, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Laboratory of Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Heart & Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, ON, Canada; Ajmera Transplant Center, University Health Network, Toronto, ON, Canada. Electronic address:
People with type 2 diabetes (T2D) are at a higher risk for myocardial infarction (MI) than age-matched healthy individuals. Here, we studied cell-based cardiac regeneration post MI in T2D rats modeling the co-morbid conditions in patients with MI. We recapitulated the T2D hallmarks and clinical aspects of diabetic cardiomyopathy using high-fat diet and streptozotocin in athymic rats, which were then subjected to MI and intramyocardial implantation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with or without rat adipose-derived microvessels (MVs).
View Article and Find Full Text PDFPLoS One
January 2025
Department of Otolaryngology-Head and Neck Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
Objective: What we hear may influence postural control, particularly in people with vestibular hypofunction. Would hearing a moving subway destabilize people similarly to seeing the train move? We investigated how people with unilateral vestibular hypofunction and healthy controls incorporated broadband and real-recorded sounds with visual load for balance in an immersive contextual scene.
Design: Participants stood on foam placed on a force-platform, wore the HTC Vive headset, and observed an immersive subway environment.
J Neurophysiol
February 2025
Breathing Research and Therapeutics Center, Department of Physical Therapy, University of Florida, Gainesville, Florida, United States.
We present a case report of a 42-year-old female with post-West Nile virus meningoencephalitis who exhibited unique, long-latency diaphragm potentials evoked by transcranial and cervical magnetic stimulation after exposure to acute intermittent hypoxia (AIH). The subject was recruited for a study investigating AIH effects on respiratory motor function in healthy individuals. She had contracted West Nile virus infection 5 years before assessment that resulted in hospitalization and persistent allodynia but was not reported to the research team.
View Article and Find Full Text PDFStem Cell Rev Rep
January 2025
Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Human-induced pluripotent stem cell (hiPSC) technology has been applied in pathogenesis studies, drug screening, tissue engineering, and stem cell therapy, and patient-specific hiPSC-derived cardiomyocytes (hiPSC-CMs) have shown promise in disease modeling, including diabetic cardiomyopathy. High glucose (HG) treatment induces lipotoxicity in hiPSC-CMs, as evidenced by changes in cell size, beating rate, calcium handling, and lipid accumulation. Empagliflozin, an SGLT2 inhibitor, effectively mitigates the hypertrophic changes, abnormal calcium handling, and contractility impairment induced by HG.
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