Journal of Molecular and Cellular Cardiology This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Remodelling of potassium currents underlies arrhythmic action potential prolongation under beta-adrenergic stimulation in hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy (HCM) patients often present an enhanced arrhythmogenicity that can lead to lethal arrhythmias, especially during exercise. Recent studies have indicated an abnormal response of HCM cardiomyocytes to β-adrenergic receptor stimulation (β-ARS), with prolongation of their action potential rather than shortening. The mechanisms underlying this aberrant response to sympathetic stimulation and its possible proarrhythmic role remain unknown. The aims of this study are to investigate the key ionic mec hanisms underlying the HCM abnormal response to β-ARS and the resultant repolarisation abnormalities...
Source: Journal of Molecular and Cellular Cardiology - September 1, 2022 Category: Cytology Authors: Ruben Doste, Raffaele Coppini, Alfonso Bueno-Orovio Source Type: research

Mechanisms and strategies to promote cardiac xenotransplantation
End stage heart failure is a terminal disease, and the only curative therapy is orthotopic heart transplantation. Due to limited organ availability, alternative strategies have received intense interest for treatment of patients with advanced heart failure. Recent studies using gene-edited porcine organs suggest that cardiac xenotransplantation may provide a future source of organs. In this review, we highlight the historical milestones for cardiac xenotransplantation and the gene editing strategies designed to overcome immunological barriers, which have culminated in a recent cardiac pig-to-human xenotransplant. (Source: ...
Source: Journal of Molecular and Cellular Cardiology - August 28, 2022 Category: Cytology Authors: Daniel J. Garry, Joshua I. Weiner, Sarah M. Greising, Mary G. Garry, David H. Sachs Source Type: research

Elucidating the role of the L-type calcium channel in excitability and energetics in the heart: The ISHR 2020 Research Achievement Award Lecture
Cardiovascular disease continues to be the leading health burden worldwide and with the rising rates in obesity and type II diabetes and ongoing effects of long COVID, it is anticipated that the burden of cardiovascular morbidity and mortality will increase. Calcium is essential to cardiac excitation and contraction. The main route for Ca2+ influx is the L-type Ca2+ channel (Cav1.2) and embryos that are homozygous null for the Cav1.2 gene are lethal at day 14 postcoitum. Acute changes in Ca2+ influx through the channel contribute to arrhythmia and sudden death, and chronic increases in intracellular Ca2+ contribute to path...
Source: Journal of Molecular and Cellular Cardiology - August 27, 2022 Category: Cytology Authors: Livia C. Hool Tags: Review article Source Type: research

Enhanced calcium release at specialised surface sites compensates for reduced t-tubule density in neonatal sheep atrial myocytes
Cardiac myocytes rely on transverse (t)-tubules to facilitate a rapid rise in calcium throughout the cell. However, despite their importance in triggering synchronous Ca2+ release, t-tubules are highly labile structures. They develop postnatally, increase in density during exercise training and are lost in diseases such as heart failure (HF). In the majority of settings, an absence of t-tubules decreases function. Here we show that despite reduced t-tubule density due to immature t-tubules, the newborn atrium is highly specialised to maintain Ca2+ release. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - August 26, 2022 Category: Cytology Authors: Charlotte E.R. Smith, Christian Pinali, David A. Eisner, Andrew W. Trafford, Katharine M. Dibb Source Type: research

The heart of cardiac reprogramming: The cardiac fibroblasts
Cardiovascular disease is the leading cause of death worldwide, outpacing pulmonary disease, infectious disease, and all forms of cancer. Myocardial infarction (MI) dominates cardiovascular disease, contributing to four out of five cardiovascular related deaths. Following MI, patients suffer adverse and irreversible myocardial remodeling associated with cardiomyocyte loss and infiltration of fibrotic scar tissue. Current therapies following MI only mitigate the cardiac physiological decline rather than restore damaged myocardium function. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - August 22, 2022 Category: Cytology Authors: Shea N. Ricketts, Li Qian Tags: Review article Source Type: research

Glutamine uptake and catabolism is required for myofibroblast formation and persistence
Fibrosis and extracellular matrix remodeling are mediated by resident cardiac fibroblasts (CFs). In response to injury, fibroblasts activate, differentiating into specialized synthetic and contractile myofibroblasts producing copious extracellular matrix proteins (e.g., collagens). Myofibroblast persistence in chronic diseases, such as HF, leads to progressive cardiac dysfunction and maladaptive remodeling. We recently reported that an increase in αKG (alpha-ketoglutarate) bioavailability, which contributes to enhanced αKG-dependent lysine demethylase activity and chromatin remodeling, is required for myofibroblast forma...
Source: Journal of Molecular and Cellular Cardiology - August 18, 2022 Category: Cytology Authors: Andrew A. Gibb, Anh T. Huynh, Ryan B. Gaspar, Tori L. Ploesch, Alyssa A. Lombardi, Pawel K. Lorkiewicz, Michael P. Lazaropoulos, Ken Bedi, Zolt Arany, Kenneth B. Margulies, Bradford G. Hill, John W. Elrod Source Type: research

A perinuclear calcium compartment regulates cardiac myocyte hypertrophy
The pleiotropic Ca2+/calmodulin-dependent phosphatase calcineurin is a key regulator of pathological cardiac myocyte hypertrophy. The selective activation of hypertrophic calcineurin signaling under stress conditions has been attributed to compartmentation of Ca2+ signaling in cardiac myocytes. Here, perinuclear signalosomes organized by the scaffold protein muscle A-Kinase Anchoring Protein β (mAKAPβ/AKAP6β) are shown to orchestrate local Ca2+ transients, inducing calcineurin-dependent NFATc nuclear localization and myocyte hypertrophy in response to β-adrenergic receptor activation. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - August 8, 2022 Category: Cytology Authors: Moriah Gildart Turcotte, Hrishikesh Thakur, Michael S. Kapiloff, Kimberly L. Dodge-Kafka Source Type: research

PGE2 protects against heart failure through inhibiting TGF- β1 synthesis in cardiomyocytes and crosstalk between TGF-β1 and GRK2
Inflammation plays a central role in the development of heart failure. Prostaglandin E2 (PGE2) is a key mediator of the inflammatory process in the cardiovascular system. However, the role of PGE2 in heart failure is complex and controversial. A recent report suggested that PGE2 inhibits acute β adrenergic receptor (β-AR) stimulation-enhanced cardiac contractility. The aim of this study was to characterize the influence of PGE2 on chronic β-AR stimulation-induced heart failure. Male C57BL/6 J mice received isoproterenol (ISO) or vehicle for 4 weeks. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - August 4, 2022 Category: Cytology Authors: Jing Fu, Li Li, Long Chen, Congping Su, Xiuling Feng, Kai Huang, Laxi Zhang, Xiaoyan Yang, Qin Fu Source Type: research

Cardiomyocyte-specific loss of plasma membrane calcium ATPase 1 impacts cardiac rhythm and is associated with ventricular repolarisation dysfunction
Plasma membrane calcium ATPase 1 (PMCA1, Atp2b1) is emerging as a key contributor to cardiac physiology, involved in calcium handling and myocardial signalling. In addition, genome wide association studies have associated PMCA1 in several areas of cardiovascular disease including hypertension and myocardial infarction. Here, we investigated the role of PMCA1 in basal cardiac function and heart rhythm stability. Cardiac structure, heart rhythm and arrhythmia susceptibility were assessed in a cardiomyocyte-specific PMCA1 deletion (PMCA1CKO) mouse model. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - July 31, 2022 Category: Cytology Authors: Claire Wilson, Nick Stafford, Min Zi, Alexandru Chelu, Barbara C. Niort, Yatong Li, Florence Baudoin, Sukhpal Prehar, Andrew W. Trafford, Elizabeth J. Cartwright Source Type: research

Improved Ca2+ release synchrony following selective modification of Itof and phase 1 repolarization in normal and failing ventricular myocytes
Loss of ventricular action potential (AP) early phase 1 repolarization may contribute to the impaired Ca2+ release and increased risk of sudden cardiac death in heart failure. Therefore, restoring AP phase 1 by augmenting the fast transient outward K+ current (Itof) might be beneficial, but direct experimental evidence to support this proposition in failing cardiomyocytes is limited. Dynamic clamp was used to selectively modulate the contribution of Itof to the AP and Ca2+ transient in both normal (guinea pig and rabbit) and in failing rabbit cardiac myocytes. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - July 28, 2022 Category: Cytology Authors: Ewan D. Fowler, Nan Wang, Melanie J. Hezzell, Guillaume Chanoit, Jules C. Hancox, Mark B. Cannell Source Type: research

“The monster in the closet is real”
A mountain of evidence suggests low cardiac thyroid hormone function in patients with heart diseases is common, including many with normal serum hormone levels [1]. This condition likely has a major adverse effect on long-term outcomes. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - July 26, 2022 Category: Cytology Authors: A. Martin Gerdes Tags: Letter to the editor Source Type: research

Mosaicism for the smooth muscle cell (SMC)-specific knock-in of the Acta2 R179C pathogenic variant: Implications for gene editing therapies
Pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections (TAD). De novo heterozygous ACTA2 variants disrupting arginine 179 cause Smooth Muscle Dysfunction Syndrome (SMDS), characterized by childhood onset TAD and cerebrovascular disease, with disruption of other smooth muscle cell (SMC)-dependent systems [1,2]. Because the human and mouse genes encode α-SMA with identical amino acid sequence, we sought to establish a SMDS mouse model to determine how this alteration causes a more severe phenotype than other ACTA2 mutations. (Source: Journal of Molecul...
Source: Journal of Molecular and Cellular Cardiology - July 22, 2022 Category: Cytology Authors: Anita Kaw, Albert J. Pedroza, Abhijnan Chattopadhyay, Amelie Pinard, Dongchuan Guo, Kaveeta Kaw, Zhen Zhou, Rohan Shad, Michael P. Fischbein, Callie S. Kwartler, Dianna M. Milewicz Tags: Letter to the editor Source Type: research

GRK2 in cardiovascular disease and its potential as a therapeutic target
Cardiovascular diseases (CVDs) represent the leading cause of death globally. Despite major advances in the field of pharmacological CVD treatments, particularly in the field of heart failure (HF) research, case numbers and overall mortality remain high and have trended upwards over the last few years. Thus, identifying novel molecular targets for developing HF therapeutics remains a key research focus. G protein-coupled receptors (GPCRs) are critical myocardial signal transducers which regulate cardiac contractility, growth, adaptation and metabolism. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - July 22, 2022 Category: Cytology Authors: Kimberly M. Ferrero, Walter J. Koch Tags: Review article Source Type: research

Integrins in cardiac fibrosis
Cells sense mechanical stress and changes in their matrix environment through the integrins, a family of heterodimeric surface receptors that bind to extracellular matrix ligands and trigger cytoskeletal remodeling, while transducing a wide range of intracellular signals. Integrins have been extensively implicated in regulation of inflammation, repair and fibrosis in many different tissues. This review manuscript discusses the role of integrin-mediated cascades in myocardial fibrosis. In vitro studies have demonstrated that β1 and αv integrins play an important role in fibrogenic conversion of cardiac fibroblast, acting ...
Source: Journal of Molecular and Cellular Cardiology - July 21, 2022 Category: Cytology Authors: Ruoshui Li, Nikolaos G. Frangogiannis Tags: Review article Source Type: research

Is epicardial adipose tissue a key pathophysiologic target in heart failure with preserved ejection?
The epicardial adipose tissue (EAT) is a visceral fat deposit that covers up to 80% of the heart surface and can constitute up to 20% of total cardiac mass. The EAT and myocardium both originate from the splanchnic mesoderm, and due to their shared embryology have a common blood supply with no fascia separating the EAT from the myocardium. In terms of blood supply, ontogenetic origin and transcriptome, EAT differs from other visceral and subcutaneous fat depots [1]. As a result of approximation and shared blood supply, the EAT can have a direct (bidirectional) paracrine effect on the myocardium potentially influencing card...
Source: Journal of Molecular and Cellular Cardiology - July 19, 2022 Category: Cytology Authors: Pieter Martens, Christopher Nguyen, W.H. Wilson Tang Tags: Letter to the editor Source Type: research