CineCT platform for in vivo and ex vivo measurement of 3D high resolution Lagrangian strains in the left ventricle following myocardial infarction and intramyocardial delivery of theranostic hydrogel
Myocardial infarction (MI) produces acute changes in strain and stiffness within the infarct that can affect remote areas of the left ventricle (LV) and drive pathological remodeling. We hypothesized that intramyocardial delivery of a hydrogel within the MI region would lower wall stress and reduce adverse remodeling in Yorkshire pigs (n  = 5). 99mTc-Tetrofosmin SPECT imaging defined the location and geometry of induced MI and border regions in pigs, and in vivo and ex vivo contrast cine computed tomography (cineCT) quantified deformations of the LV myocardium. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - February 25, 2022 Category: Cytology Authors: D.E. Midgett, S.L. Thorn, S.S. Ahn, S. Uman, R. Avendano, I. Melvinsdottir, T. Lysyy, S. Kim, J.S. Duncan, J.D. Humphrey, X. Papademetris, J.A. Burdick, A.J. Sinusas Source Type: research

Human cardiac myosin-binding protein C phosphorylation- and mutation-dependent structural dynamics monitored by time-resolved FRET
Cardiac myosin-binding protein C (cMyBP-C) is a thick filament-associated protein of the sarcomere and a potential therapeutic target for treating contractile dysfunction in heart failure. Mimicking the structural dynamics of phosphorylated cMyBP-C by small-molecule drug binding could lead to therapies that modulate cMyBP-C conformational states, and thereby function, to improve contractility. We have developed a human cMyBP-C biosensor capable of detecting intramolecular structural changes due to phosphorylation and mutation. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - February 25, 2022 Category: Cytology Authors: Rhye-Samuel Kanassatega, Thomas A. Bunch, Victoria C. Lepak, Christopher Wang, Brett A. Colson Source Type: research

Changes in extracellular matrix in failing human non-ischemic and ischemic hearts with mechanical unloading
Ischemic and non-ischemic cardiomyopathies have distinct etiologies and underlying disease mechanisms, which require in-depth investigation for improved therapeutic interventions. The goal of this study was to use clinically obtained myocardium from healthy and heart failure patients, and characterize the changes in extracellular matrix (ECM) in ischemic and non-ischemic failing hearts, with and without mechanical unloading. Using tissue engineering methodologies, we also investigated how diseased human ECM, in the absence of systemic factors, can influence cardiomyocyte function. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - February 24, 2022 Category: Cytology Authors: Yimu Zhao, Amandine Godier-Furnemont, Noortje A.M. Bax, Carlijn V.C. Bouten, Lewis M. Brown, Barry Fine, Gordana Vunjak-Novakovic Source Type: research

Ion channels in stem cells and their roles in stem cell biology and vascular diseases
Stem cell therapy may be a promising option for the treatment of vascular diseases. In recent years, significant progress has been made in stem cell research, especially in the mechanism of stem cell activation, homing and differentiation in vascular repair and reconstruction. Current research on stem cells focuses on protein expression and transcriptional networks. Ion channels are considered to be the basis for the generation of bioelectrical signals, which control the proliferation, differentiation and migration of various cell types. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - February 7, 2022 Category: Cytology Authors: Min Zhang, Chang Che, Jun Cheng, Pengyun Li, Yan Yang Source Type: research

The harder the climb the better the view: The impact of substrate stiffness on cardiomyocyte fate
The quest for novel methods to mature human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for cardiac regeneration, modelling and drug testing has emphasized a need to create microenvironments with physiological features. Many studies have reported on how cardiomyocytes sense substrate stiffness and adapt their morphological and functional properties. However, these observations have raised new biological questions and a shared vision to translate it into a tissue or organ context is still elusive. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - February 6, 2022 Category: Cytology Authors: Silvia Querceto, Rosaria Santoro, Aoife Gowran, Bruno Grandinetti, Giulio Pompilio, Michael Regnier, Chiara Tesi, Corrado Poggesi, Cecilia Ferrantini, Jos è Manuel Pioner Source Type: research

Benefits in cardiac function by CD38 suppression: Improvement in NAD+ levels, exercise capacity, heart rate variability and protection against catecholamine induced ventricular arrhythmias
CD38 enzymatic activity regulates NAD+ and cADPR levels in mammalian tissues, and therefore has a prominent role in cellular metabolism and calcium homeostasis. Consequently, it is reasonable to hypothesize about its involvement in cardiovascular physiology as well as in heart related pathological conditions. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - January 31, 2022 Category: Cytology Authors: Guillermo Agorrody, Thais R. Peclat, Gonzalo Peluso, Luis A. Gonano, Leonardo Santos, Wim van Schooten, Claudia C.S. Chini, Carlos Escande, Eduardo N. Chini, Paola Contreras Source Type: research

Increased atrial effectiveness of flecainide conferred by altered biophysical properties of sodium channels
Atrial fibrillation (AF) affects over 1% of the population and is a leading cause of stroke and heart failure in the elderly. A feared side effect of sodium channel blocker therapy, ventricular pro-arrhythmia, appears to be relatively rare in patients with AF. The biophysical reasons for this relative safety of sodium blockers are not known.Our data demonstrates intrinsic differences between atrial and ventricular cardiac voltage-gated sodium currents (INa), leading to reduced maximum upstroke velocity of action potential and slower conduction, in left atria compared to ventricle. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - January 31, 2022 Category: Cytology Authors: Sian O' Brien, Andrew P. Holmes, Daniel M. Johnson, S. Nashitha Kabir, Christopher O' Shea, Molly O' Reilly, Adelisa Avezzu, Jasmeet S. Reyat, Amelia W. Hall, Clara Apicella, Patrick T. Ellinor, Steven Niederer, Nathan R. Tucker, Larissa Fabritz, Paulus K Source Type: research

The nuclear receptor co-repressor 1 is a novel cardioprotective factor against acute myocardial ischemia-reperfusion injury
Acute myocardial ischemia/reperfusion (MI/R) is a major determinant of prognosis in myocardial infarction patients, while effective therapies are currently lacking. Nuclear receptor co-repressor 1 (NCoR1) is emerging as a critical regulator of cell survival and death signaling in mammals. However, the role of NCoR1 in the pathogenesis of acute MI/R injury remains unknown. Here, we observed that NCoR1 was highly expressed in the mouse heart and significantly downregulated after acute MI/R injury. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - January 23, 2022 Category: Cytology Authors: Zihan Qin, Lingchen Gao, Guanqiao Lin, Hong Zhu, Yingmin Chen, Fangyuan Zhong, Hongmei Zhou, Shengzhong Duan, Jun Pu Source Type: research

Human engineered heart tissue transplantation in a guinea pig chronic injury model
Myocardial injury leads to an irreversible loss of cardiomyocytes (CM). The implantation of human engineered heart tissue (EHT) has become a promising regenerative approach. Previous studies exhibited beneficial, dose-dependent effects of human induced pluripotent stem cell (hiPSC)-derived EHT patch transplantation in a guinea pig model in the subacute phase of myocardial injury. Yet, advanced heart failure often results from a chronic remodeling process. Therefore, from a clinical standpoint it is worthwhile to explore the ability to repair the chronically injured heart. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - January 23, 2022 Category: Cytology Authors: Constantin von Bibra, Aya Shibamiya, Birgit Geertz, Eva Querdel, Maria K öhne, Tim Stuedemann, Jutta Starbatty, Felix N. Schmidt, Arne Hansen, Bernhard Hiebl, Thomas Eschenhagen, Florian Weinberger Source Type: research

The essential role for endothelial cell sprouting in coronary collateral growth
Coronary collateral growth is a natural bypass for ischemic heart diseases. It offers tremendous therapeutic benefit, but the process of coronary collateral growth is incompletely understood due to limited preclinical murine models that would enable interrogation of its mechanisms and processes via genetic modification and lineage tracing. Understanding the processes by which coronary collaterals develop can unlock new therapeutic strategies for ischemic heart disease. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - January 21, 2022 Category: Cytology Authors: Anurag Jamaiyar, Cody Juguilon, Weiguo Wan, Devan Richardson, Sofia Chinchilla, James Gadd, Molly Enrick, Tao Wang, Caige McCabe, Yang Wang, Chris Kolz, Alyssa Clark, Sathwika Thodeti, Vahagn Ohanyan, Feng Dong, Bin Zhou, William Chilian, Liya Yin Source Type: research

RBM20S639G mutation is a high genetic risk factor for premature death through RNA-protein condensates
In this study, we generated a RBM20 S639G mutation knock-in (KI) mouse model to validate the function of S639G mutation and examine the underlying mechanisms. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - January 15, 2022 Category: Cytology Authors: Chunyan Wang, Yanghai Zhang, Mei Methawasin, Camila Urbano Braz, Jeffrey Gao-Hu, Betty Yang, Joshua Strom, Jochen Gohlke, Timothy Hacker, Hasan Khatib, Henk Granzier, Wei Guo Source Type: research

A junctional cAMP compartment regulates rapid Ca2+ signaling in atrial myocytes
Axial tubule junctions with the sarcoplasmic reticulum control the rapid intracellular Ca2+-induced Ca2+ release that initiates atrial contraction. In atrial myocytes we previously identified a constitutively increased ryanodine receptor (RyR2) phosphorylation at junctional Ca2+ release sites, whereas non-junctional RyR2 clusters were phosphorylated acutely following β-adrenergic stimulation. Here, we hypothesized that the baseline synthesis of 3′,5′-cyclic adenosine monophosphate (cAMP) is constitutively augmented in the axial tubule junctional compartments of atrial myocytes. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - January 13, 2022 Category: Cytology Authors: S ören Brandenburg, Jan Pawlowitz, Vanessa Steckmeister, Hariharan Subramanian, Dennis Uhlenkamp, Marina Scardigli, Mufassra Mushtaq, Saskia I. Amlaz, Tobias Kohl, Jörg W. Wegener, Demetrios A. Arvanitis, Despina Sanoudou, Leonardo Sacconi, Gerd Hasenfu Source Type: research

Shortening the thick filament by partial deletion of titin's C-zone alters cardiac function by reducing the operating sarcomere length range
Titin's C-zone is an inextensible segment in titin, comprised of 11 super-repeats and located in the cMyBP-C-containing region of the thick filament. Previously we showed that deletion of titin's super-repeats C1 and C2 (Ttn ΔC1–2 model) results in shorter thick filaments and contractile dysfunction of the left ventricular (LV) chamber but that unexpectedly LV diastolic stiffness is normal. Here we studied the contraction-relaxation kinetics from the time-varying elastance of the LV and intact cardiomyocyte, cellular work loops of intact cardiomyocytes, Ca2+ transients, cross-bridge kinetics, and myofilament Ca2+ sensit...
Source: Journal of Molecular and Cellular Cardiology - January 10, 2022 Category: Cytology Authors: Mei Methawasin, Gerrie P. Farman, Shawtaroh Granzier-Nakajima, Joshua Strom, Balazs Kiss, John E. Smith, Henk Granzier Source Type: research

Mitochondrial protein hyperacetylation underpins heart failure with preserved ejection fraction in mice
This study was designed to investigate the metabolic signature of HFpEF and test the potential therapeutic intervention in a mouse model. By utilizing a “3-Hit” HFpEF mouse model, we observed a global protein hyperacetylation in the HFpEF hearts as compared to the pressure overload-induced HFrEF and adult/aged non-heart failure (NHF) hearts. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - January 5, 2022 Category: Cytology Authors: Xin Liu, Yabing Zhang, Yan Deng, Lin Yang, Wei Ou, Maodi Xie, Lin Ding, Chunling Jiang, Hai Yu, Qian Li, Tao Li Source Type: research

Phosphodiesterase type 4 anchoring regulates cAMP signaling to Popeye domain-containing proteins
Cyclic AMP is a ubiquitous second messenger used to transduce intracellular signals from a variety of Gs-coupled receptors. Compartmentalisation of protein intermediates within the cAMP signaling pathway underpins receptor-specific responses. The cAMP effector proteins protein-kinase A and EPAC are found in complexes that also contain phosphodiesterases whose presence ensures a coordinated cellular response to receptor activation events. Popeye domain containing (POPDC) proteins are the most recent class of cAMP effectors to be identified and have crucial roles in cardiac pacemaking and conduction. (Source: Journal of Mole...
Source: Journal of Molecular and Cellular Cardiology - January 5, 2022 Category: Cytology Authors: Amy J. Tibbo, Delphine Mika, Sara Dobi, Jiayue Ling, Aisling McFall, Gonzalo S. Tejeda, Connor Blair, Ruth MacLeod, Niall MacQuaide, Caglar G ök, William Fuller, Brian O. Smith, Godfrey L. Smith, Grégoire Vandecasteele, Thomas Brand, George S. Baillie Source Type: research