C166 EVs potentiate miR cardiac reprogramming via miR-148a-3p
We have demonstrated that directly reprogramming cardiac fibroblasts into new cardiomyocytes via miR combo improves cardiac function in the infarcted heart. However, major challenges exist with delivery and efficacy. During a screening based approach to improve delivery, we discovered that C166-derived EVs were effective delivery agents for miR combo both in vitro and in vivo. In the latter, EV mediated delivery of miR combo induced significant conversion of cardiac fibroblasts into cardiomyocytes (~20%), reduced fibrosis and improved cardiac function in a myocardial infarction injury model. (Source: Journal of Molecular a...
Source: Journal of Molecular and Cellular Cardiology - April 4, 2024 Category: Cytology Authors: Hualing Sun, Xinghua Wang, Richard E. Pratt, Victor J. Dzau, Conrad P. Hodgkinson Source Type: research

Reduced cardiac antioxidant defenses mediate increased susceptibility to workload-induced myocardial injury in males with genetic cardiomyopathy
Ongoing cardiomyocyte injury is a major mechanism in the progression of heart failure, particularly in dystrophic hearts. Due to the poor regenerative capacity of the adult heart, cardiomyocyte death results in the permanent loss of functional myocardium. Understanding the factors contributing to myocyte injury is essential for the development of effective heart failure therapies. As a model of persistent cardiac injury, we examined mice lacking β-sarcoglycan (β-SG), a key component of the dystrophin glycoprotein complex (DGC). (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - March 23, 2024 Category: Cytology Authors: Tatyana A. Vetter, Preethy Parthiban, Jackie A. Stevens, Xavier S. Revelo, Mark J. Kohr, DeWayne Townsend Source Type: research

Atrial proteomic profiling reveals a switch towards profibrotic gene expression program in CREM-Ib ΔC-X mice with persistent atrial fibrillation
Overexpression of the CREM (cAMP response element-binding modulator) isoform CREM-Ib ΔC-X in transgenic mice (CREM-Tg) causes the age-dependent development of spontaneous AF. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - March 19, 2024 Category: Cytology Authors: Shuai Zhao, Mohit M. Hulsurkar, Satadru K. Lahiri, Yuriana Aguilar-Sanchez, Elda Munivez, Frank Ulrich M üller, Antrix Jain, Anna Malovannaya, Kendrick Yiu, Svetlana Reilly, Xander H.T. Wehrens Source Type: research

Myocardial glycophagy flux dysregulation and glycogen accumulation characterize diabetic cardiomyopathy
Diabetic heart disease morbidity and mortality is escalating. No specific therapeutics exist and mechanistic understanding of diabetic cardiomyopathy etiology is lacking. While lipid accumulation is a recognized cardiomyocyte phenotype of diabetes, less is known about glycolytic fuel handling and storage. Based on in vitro studies, we postulated the operation of an autophagy pathway in the myocardium specific for glycogen homeostasis – glycophagy. Here we visualize occurrence of cardiac glycophagy and show that the diabetic myocardium is characterized by marked glycogen elevation and altered cardiomyocyte glycogen locali...
Source: Journal of Molecular and Cellular Cardiology - March 13, 2024 Category: Cytology Authors: Kimberley M. Mellor, Upasna Varma, Parisa Koutsifeli, Lorna J. Daniels, Victoria L. Benson, Marco Annandale, Xun Li, Yohanes Nursalim, Johannes V. Janssens, Kate L. Weeks, Kim L. Powell, Terence J. O'Brien, Rajesh Katare, Rebecca H. Ritchie, James R. Bell Source Type: research

Translating myosin-binding protein C and titin abnormalities to whole-heart function using a novel calcium-contraction coupling model
Mutations in cardiac myosin-binding protein C (cMyBP-C) or titin may respectively lead to hypertrophic (HCM) or dilated (DCM) cardiomyopathies. The mechanisms leading to these phenotypes remain unclear because of the challenge of translating cellular abnormalities to whole-heart and system function.We developed and validated a novel computer model of calcium-contraction coupling incorporating the role of cMyBP-C and titin based on the key assumptions: 1) tension in the thick filament promotes cross-bridge attachment mechanochemically, 2) with increasing titin tension, more myosin heads are unlocked for attachment, and 3) c...
Source: Journal of Molecular and Cellular Cardiology - March 8, 2024 Category: Cytology Authors: Theo Arts, Aurore Lyon, Tammo Delhaas, Diederik W.D. Kuster, Jolanda van der Velden, Joost Lumens Source Type: research

Cellular nucleic acid binding protein facilitates cardiac repair after myocardial infarction by activating β-catenin signaling
The regenerative capacity of the adult mammalian heart is limited, while the neonatal heart is an organ with regenerative and proliferative ability. Activating adult cardiomyocytes (CMs) to re-enter the cell cycle is an effective therapeutic method for ischemic heart disease such as myocardial infarction (MI) and heart failure. Here, we aimed to reveal the role and potential mechanisms of cellular nucleic acid binding protein (CNBP) in cardiac regeneration and repair after heart injury. CNBP is highly expressed within 7  days post-birth while decreases significantly with the loss of regenerative ability. (Source: Journal...
Source: Journal of Molecular and Cellular Cardiology - March 1, 2024 Category: Cytology Authors: Chong Du, Shan Zhao, Tiankai Shan, Xudong Han, Qiqi Jiang, Jiawen Chen, Lingfeng Gu, Tianwen Wei, Tongtong Yang, Sibo Wang, Hao Wang, Xuejiang Guo, Liansheng Wang Source Type: research

ATF6 protects against protein misfolding during cardiac hypertrophy
Cardiomyocytes activate the unfolded protein response (UPR) transcription factor ATF6 during pressure overload-induced hypertrophic growth. The UPR is thought to increase ER protein folding capacity and maintain proteostasis. ATF6 deficiency during pressure overload leads to heart failure, suggesting that ATF6 protects against myocardial dysfunction by preventing protein misfolding. However, conclusive evidence that ATF6 prevents toxic protein misfolding during cardiac hypertrophy is still pending. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - February 23, 2024 Category: Cytology Authors: Christoph Hofmann, Marjan Aghajani, Cecily D. Alcock, Erik A. Blackwood, Clara Sandmann, Nicole Herzog, Julia Gro ß, Lars Plate, R. Luke Wiseman, Randal J. Kaufman, Hugo A. Katus, Tobias Jakobi, Mirko Völkers, Christopher C. Glembotski, Shirin Doroudgar Source Type: research

Neutrophils are indispensable for adverse cardiac remodeling in heart failure
Persistent immune activation contributes significantly to left ventricular (LV) dysfunction and adverse remodeling in heart failure (HF). In contrast to their well-known essential role in acute myocardial infarction (MI) as first responders that clear dead cells and facilitate subsequent reparative macrophage polarization, the role of neutrophils in the pathobiology of chronic ischemic HF is poorly defined. To determine the importance of neutrophils in the progression of ischemic cardiomyopathy, we measured their production, levels, and activation in a mouse model of chronic HF 8  weeks after permanent coronary artery lig...
Source: Journal of Molecular and Cellular Cardiology - February 22, 2024 Category: Cytology Authors: Sergey Antipenko, Nicolas Mayfield, Miki Jinno, Matthias Gunzer, Mohamed Ameen Ismahil, Tariq Hamid, Sumanth D. Prabhu, Gregg Rokosh Source Type: research

Gut microbial metabolite trimethylamine N-oxide induces aortic dissection
This study aimed to explore the effects of TMAO on AD. Plasma and fecal samples from patients with AD and healthy individuals were collected to analyze TMAO levels and gut microbial species, respectively. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - February 21, 2024 Category: Cytology Authors: Shan Huang, Shijuan Gao, Yihui Shao, Ping Li, Jie Lu, Ke Xu, Zeyi Zhou, Yulin Li, Jie Du Source Type: research

Novel roles of cardiac-derived erythropoietin in cardiac development and function
The role of erythropoietin (EPO) has extended beyond hematopoiesis to include cytoprotection, inotropy, and neurogenesis. Extra-renal EPO has been reported for multiple tissue/cell types, but the physiological relevance remains unknown. Although the EPO receptor is expressed by multiple cardiac cell types and human recombinant EPO increases contractility and confers cytoprotection against injury, whether the heart produces physiologically meaningful amounts of EPO in vivo is unclear. We show a distinct circadian rhythm of cardiac EPO mRNA expression in adult mice and increased mRNA expression during embryogenesis, suggesti...
Source: Journal of Molecular and Cellular Cardiology - February 20, 2024 Category: Cytology Authors: Melissa A. Allwood, Brittany A. Edgett, Mathew J. Platt, Jade P. Marrow, Bridget Coyle-Asbil, Emma J.B. Holjak, Victoria L. Nelson, Swara Bangali, Razan Alshamali, Kathy Jacyniak, Jorden M. Klein, Laura Farquharson, Nadya Romanova, Victoria Northrup, Lesl Source Type: research

Cannabidiol protects against acute aortic dissection by inhibiting macrophage infiltration and PMAIP1-induced vascular smooth muscle cell apoptosis
Acute aortic dissection (AAD) progresses rapidly and is associated with high mortality; therefore, there remains an urgent need for pharmacological agents that can protect against AAD. Herein, we examined the therapeutic effects of cannabidiol (CBD) in AAD by establishing a suitable mouse model. In addition, we performed human AAD single-cell RNA sequencing and mouse AAD bulk RNA sequencing to elucidate the potential underlying mechanism of CBD. Pathological assays and in vitro studies were performed to verify the results of the bioinformatic analysis and explore the pharmacological function of CBD. (Source: Journal of Mol...
Source: Journal of Molecular and Cellular Cardiology - February 20, 2024 Category: Cytology Authors: Yilong Guo, Yang Che, Xuelin Zhang, Zongna Ren, Yinan Chen, Liliang Guo, Lin Mao, Ren Wei, Xiang Gao, Tao Zhang, Li Wang, Wei Guo Source Type: research

Exercise reduces pro-inflammatory lipids and preserves resolution mediators that calibrate macrophage-centric immune metabolism in spleen and heart following obesogenic diet in aging mice
The study investigated the role of volunteer exercise and an obesogenic diet (OBD) in mice, focusing on the splenocardiac axis and inflammation-resolution signaling. Male C57BL/6J mice (2  months old) were assigned to control (CON) or OBD groups for ten months, then randomized into sedentary (Sed) or exercise (Exe) groups for two weeks. Leukocytes, heart function, structure, and spleen tissue examined for inflammation-resolution mediators and macrophage-centric gene transcripts. Aft er two weeks of volunteer exercise, cardiac function shows limited changes, but structural changes were notable in the heart and spleen. (Sou...
Source: Journal of Molecular and Cellular Cardiology - February 15, 2024 Category: Cytology Authors: Ganesh V. Halade, Gunjan Upadhyay, MathanKumar Marimuthu, Xuan Wanling, Vasundhara Kain Source Type: research

NCoR1 limits angiogenic capacity by altering Notch signaling
Corepressors negatively regulate gene expression by chromatin compaction. Targeted regulation of gene expression could provide a means to control endothelial cell phenotype. We hypothesize that by targeting corepressor proteins, endothelial angiogenic function can be improved. To study this, the expression and function of nuclear corepressors in human umbilical vein endothelial cells (HUVEC) and in murine organ culture was studied. RNA-seq revealed that nuclear receptor corepressor 1 (NCoR1), silencing mediator of retinoid and thyroid hormone receptors (SMRT) and repressor element-1 silencing transcription factor (REST) ar...
Source: Journal of Molecular and Cellular Cardiology - February 15, 2024 Category: Cytology Authors: Tom Teichmann, Pedro Malacarne, Simonida Zehr, Stefan G ünther, Beatrice Pflüger-Müller, Timothy Warwick, Ralf P. Brandes Source Type: research

Exercise reduces pro-inflammatory lipids and preserves r`esolution mediators that calibrate macrophage-centric immune metabolism in spleen and heart following obesogenic diet in aging mice
The study investigated the role of volunteer exercise and an obesogenic diet (OBD) in mice, focusing on the splenocardiac axis and inflammation-resolution signaling. Male C57BL/6J mice (2  months old) were assigned to control (CON) or OBD groups for ten months, then randomized into sedentary (Sed) or exercise (Exe) groups for two weeks. Leukocytes, heart function, structure, and spleen tissue examined for inflammation-resolution mediators and macrophage-centric gene transcripts. Aft er two weeks of volunteer exercise, cardiac function shows limited changes, but structural changes were notable in the heart and spleen. (Sou...
Source: Journal of Molecular and Cellular Cardiology - February 15, 2024 Category: Cytology Authors: Ganesh V. Halade, Gunjan Upadhyay, MathanKumar Marimuthu, Xuan Wanling, Vasundhara Kain Source Type: research

Adipocyte-mediated electrophysiological remodeling of human stem cell - derived cardiomyocytes
Adipocytes normally accumulate in the epicardial and pericardial layers around the human heart, but their infiltration into the myocardium can be proarrhythmic. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - February 9, 2024 Category: Cytology Authors: Justin Morrissette-McAlmon, William R. Xu, Roald Teuben, Kenneth R. Boheler, Leslie Tung Source Type: research