Loss of cyclophilin D prolyl isomerase activity desensitizes mitochondrial permeability transition pore opening in isolated cardiac mitochondria, but does not protect in myocardial ischemia-reperfusion injury
Cyclophilin D (CyPD) is the sole member of the cyclophilin (CyP) family of peptidyl prolyl cis-trans isomerases that resides in mitochondria. Although it is generally accepted that CyPD sensitizes opening of the mitochondrial permeability transition pore (PTP) to trigger necrotic cell death, the mechanism remains poorly understood [1,2]. Furthermore, the role of the prolyl isomerase activity of CyPD in mediating these effects remains unresolved. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - September 9, 2023 Category: Cytology Authors: Kevin M. Casin, Moises Bustamante, Georgios Amanakis, Junhui Sun, Chengyu Liu, Richard N. Kitsis, Elizabeth Murphy Tags: Letter to the editor Source Type: research

Myeloid-specific deletion of Capns1 attenuates myocardial infarction injury via restoring mitochondrial function and inhibiting inflammasome activation.
Mitochondrial dysfunction of macrophage-mediated inflammatory response plays a key pathophysiological process in myocardial infarction (MI). Calpains are a well-known family of calcium-dependent cysteine proteases that regulate a variety of processes, including cell adhesion, proliferation, and migration, as well as mitochondrial function and inflammation. CAPNS1, the common regulatory subunit of calpain-1 and 2, is essential for the stabilization and activity of the catalytic subunit. Emerging studies suggest that calpains may serve as key mediators in mitochondria and NLRP3 inflammasome. (Source: Journal of Molecular and...
Source: Journal of Molecular and Cellular Cardiology - September 8, 2023 Category: Cytology Authors: Zilong Xiao, Xiang Wei, Minghui Li, Kun Yang, Ruizhen Chen, Yangang Su, Ziqing Yu, Yixiu Liang, Junbo Ge Source Type: research

PPAR δ activation improves cardiac mitochondrial homeostasis in desmin deficient mice but does not alleviate systolic dysfunction
In this study, we sought to investigate whether pharmacological activation of PPARδ via intraperitoneal administration of the se lective ligand GW0742 could ameliorate heart failure and mitochondrial dysfunction that have been previously reported in a characterized genetic model of heart failure, the desmin null mice (Des−/−). (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - August 20, 2023 Category: Cytology Authors: Dimitra Palioura, Kyriakos Mellidis, Konstantina Ioannidou-Kabouri, Eleftheria Galatou, Eleni-Taxiarchia Mouchtouri, Rodopi Stamatiou, Panagiotis Mavrommatis-Parasidis, Emmanuel Panteris, Aimilia Varela, Constantinos Davos, Konstantinos Drosatos, Manolis Source Type: research

Tnni3k influences cardiomyocyte S-phase activity and proliferation
Cardiomyocyte proliferation is a difficult phenomenon to capture and prove. Here we employ a retrospective analysis of single cell ventricular suspensions to definitively identify cardiomyocytes that have completed cell division. Through this analysis we determined that the capacity of cardiomyocytes to re-enter the cell cycle and complete cell division after injury are separate and variable traits. Further, we provide evidence that Tnni3k definitively influences both early and final stages of the cell cycle. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - August 17, 2023 Category: Cytology Authors: Alexandra L. Purdy, Samantha K. Swift, Henry M. Sucov, Michaela Patterson Source Type: research

Human PSC-derived cardiac cells and their products: therapies for cardiac repair
Despite the dramatic improvements in the management of patients with chronic heart failure which have occurred over the last decades, some of them still exhaust conventional drug-based therapies without being eligible for more aggressive options like heart transplantation or implantation of a left ventricular assist device. Cell therapy has thus emerged as a possible means of filling this niche. Multiple cell types have now been tested both in the laboratory but also in the clinics and it is fair to acknowledge that none of the clinical trials have yet conclusively proven the efficacy of cell-based approaches. (Source: Jou...
Source: Journal of Molecular and Cellular Cardiology - August 16, 2023 Category: Cytology Authors: Philippe Menasch é Source Type: research

Exploring molecular profiles of calcification in aortic vascular smooth muscle cells and aortic valvular interstitial cells
Cardiovascular calcification can occur in vascular and valvular structures and is commonly associated with calcium deposition and tissue mineralization leading to stiffness and dysfunction. Patients with chronic kidney disease and associated hyperphosphatemia have an elevated risk for coronary artery calcification (CAC) and calcific aortic valve disease (CAVD). However, there is mounting evidence to suggest that the susceptibility and pathobiology of calcification in these two cardiovascular structures may be different, yet clinically they are similarly treated. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - August 12, 2023 Category: Cytology Authors: Julie R. Kessler, Theresa S. Bluemn, Samuel A. DeCero, Punashi Dutta, Kaitlyn Thatcher, Donna K. Mahnke, Makenna C. Knas, Hail B. Kazik, Vinal Menon, Joy Lincoln Source Type: research

Utilizing human induced pluripotent stem cells to study atrial arrhythmias in the short QT syndrome
Among the monogenic inherited causes of atrial fibrillation is the short QT syndrome (SQTS), a rare channelopathy causing atrial and ventricular arrhythmias. One of the limitations in studying the mechanisms and optimizing treatment of SQTS-related atrial arrhythmias has been the lack of relevant human atrial tissues models. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - August 12, 2023 Category: Cytology Authors: Assad Shiti, Gil Arbil, Naim Shaheen, Irit Huber, Noga Setter, Lior Gepstein Source Type: research

Musings on intrinsic cardiomyocyte cell cycle activity and myocardial regeneration
Although the myocardial renewal rate in the adult mammalian heart is quite low, recent studies have identified genetic variants which can impact the degree of cardiomyocyte cell cycle reentry. Here we use the compound interest law to model the level of regenerative growth over time in mice exhibiting different rates of cardiomyocyte cell cycle reentry following myocardial injury. The modeling suggests that the limited ability of S-phase adult cardiomyocytes to progress through cytokinesis, rather than the ability to reenter the cell cycle per se, is a major contributor to the low levels of intrinsic regenerative growth in ...
Source: Journal of Molecular and Cellular Cardiology - July 28, 2023 Category: Cytology Authors: Mark H. Soonpaa, Sean P. Reuter, Peter F. Castelluccio, Loren J. Field Source Type: research

Corrigendum to “HIC2 regulates isoform switching during maturation of the cardiovascular system” [Journal of Molecular and Cellular Cardiology volume 114 (2018) P29-37/ https://doi.org/10.1016/j.yjmcc.2017.10.007]
The authors regret that there was an error in the labelling of the axes shown in the graphs in Figs. 1b and 1c. In both cases, the x-axis label should read E9.5 KO / E9.5 WT (Log2) and not E9.5 WT / E9.5 KO WT (Log2) as originally stated. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - July 28, 2023 Category: Cytology Authors: Iain M. Dykes, Kelly Lammerts van Bueren, Peter J. Scambler Tags: Corrigendum Source Type: research

Novel signaling axis of FHOD1-RNF213-Col1 α/Col3α in the pathogenesis of hypertension-induced tunica media thickening
Hypertension-induced tunica media thickening (TMT) is the most important fundamental for the subsequent complications like stroke and cardiovascular diseases. Pathogenically, TMT originates from both vascular smooth muscle cells (VSMCs) hypertrophy due to synthesizing more amount of intracellular contractile proteins and excess secretion of extracellular matrix. However, what key molecules are involved in the pathogenesis of TMT is unknown. We hypothesize that formin homology 2 domain-containing protein 1 (FHOD1), an amply expressed mediator for assembly of thin actin filament in VSMCs, is a key regulator for the pathogene...
Source: Journal of Molecular and Cellular Cardiology - July 21, 2023 Category: Cytology Authors: Yuanyuan Chen, Yuchan Yuan, Yuhan Chen, Xueze Jiang, Xuesheng Hua, Zhiyong Chen, Julie Wang, Hua Liu, Qing Zhou, Ying Yu, Zhenwei Yang, Yi Yu, Yongqin Wang, Qunshan Wang, Yigang Li, Jie Chen, Yuepeng Wang Source Type: research

Cardiac regeneration – Past advancements, current challenges, and future directions
Cardiovascular disease is the leading cause of mortality and morbidity worldwide. Despite improvements in the standard of care for patients with heart diseases, including innovation in pharmacotherapy and surgical interventions, none have yet been proven effective to prevent the progression to heart failure. Cardiac transplantation is the last resort for patients with severe heart failure, but donor shortages remain a roadblock. Cardiac regenerative strategies include cell-based therapeutics, gene therapy, direct reprogramming of non-cardiac cells, acellular biologics, and tissue engineering methods to restore damaged hear...
Source: Journal of Molecular and Cellular Cardiology - July 21, 2023 Category: Cytology Authors: Arash Pezhouman, Ngoc B. Nguyen, Maryam Kay, Baishali Kanjilal, Iman Noshadi, Reza Ardehali Source Type: research

Ventricular differences in mitochondrial Ca2+ dynamics in murine and porcine hearts
In cardiomyocytes, mitochondria produce ~95% of the ATP required for contraction [1]. Mitochondrial Ca2+ (mtCa2+) activates matrix-localized enzymes and helps to match ATP production to demand. However, mtCa2+ overload can lead to reactive oxygen species (ROS) generation and opening of the mitochondrial permeability transition pore (mPTP), which induces cell death [1,2]. Preventing mPTP opening might be a therapeutic target for cardiovascular diseases, including right ventricle (RV) failure in pulmonary hypertension [3]. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - July 15, 2023 Category: Cytology Authors: Jae Hwi Sung, Hector Chapoy Villanueva, Feng Feng, Ariadna Araque Igualador, Kurt W. Prins, Julia C. Liu Tags: Letter to the editor Source Type: research

Re: Single-cell transcriptome analysis for characterizing primary Sca-1 positive, non-endothelial cardiac cells
Sca-1+ cells in adult hearts have been considered intrinsic stem cells that can differentiate into cardiomyocytes and repair a damaged heart [1]. However, recent research has challenged this idea by suggesting that cardiac sca-1+ cells are actually endothelial cells [2]. Despite this, other studies have indicated the existence of sca-1+ non-endothelial cells in adult hearts, specifically cardiac mesenchymal stem cells (C-MSCs), that promote angiogenesis through paracrine actions and offer therapeutic benefits [3]. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - July 14, 2023 Category: Cytology Authors: Yan Shen, Il-man Kim, Yaoliang Tang Tags: Letter to the editor Source Type: research

Metabolic flux in the driver's seat during cardiac health and disease
Cardiac function is a dynamic process that must adjust efficiently to the immediate demands of physical state and activity. So too, the metabolic support of cardiac function is a dynamic process that must respond, in time, to the demands of cardiac function and viability. Flux through metabolic pathways provides chemical energy and generates signaling molecules that regulate activity among intracellular compartments to meet these demands. Thus, flux through metabolic pathways provides a dynamic mode of support of cardiomyocytes during physiological and pathophysiological challenges. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - July 13, 2023 Category: Cytology Authors: E. Douglas Lewandowski Tags: Review article Source Type: research

Introduction to review series: Regulated necrosis programs in heart disease
Biologists have known for decades that certain cells die at specific times during the development of multicellular organisms, and such events contribute to morphogenesis. However, the underlying circuitries remained a mystery until the 1980s when a small network of genes that regulate the 131 developmental somatic cell deaths ( “programmed cell death”) in the hermaphrodite of the round worm Caenorhabditis elegans was identified (reviewed in [1]). These observations provided the first mechanistic evidence for the concept that cell death can be an actively-mediated and regulated process as opposed to merely a passive con...
Source: Journal of Molecular and Cellular Cardiology - July 13, 2023 Category: Cytology Authors: Joshua L. Axelrod, Ryan Pekson, Richard N. Kitsis Source Type: research