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.

A novel transcription factor combination for direct reprogramming to a spontaneously contracting human cardiomyocyte-like state
The reprogramming of somatic cells to a spontaneously contracting cardiomyocyte-like state using defined transcription factors has proven successful in mouse fibroblasts. However, this process has been less successful in human cells, thus limiting the potential clinical applicability of this technology in regenerative medicine. We hypothesized that this issue is due to a lack of cross-species concordance between the required transcription factor combinations for mouse and human cells. To address this issue, we identified novel transcription factor candidates to induce cell conversion between human fibroblasts and cardiomyo...
Source: Journal of Molecular and Cellular Cardiology - July 6, 2023 Category: Cytology Authors: Marisol Romero-Tejeda, Hananeh Fonoudi, Carly J. Weddle, Jean-Marc DeKeyser, Brian Lenny, K. Ashley Fetterman, Tarek Magdy, Yadav Sapkota, Conrad Epting, Paul W. Burridge Source Type: research

RyR2-stabilization therapy with dantrolene against left ventricular remodeling and lethal arrhythmia in heart failure
We read with great interest the article recently published (June 05, 2023) by Schmeckpeper et al. in the Journal of Molecular and Cellular Cardiology, supporting the notion that RyR2 stabilization with dantrolene prevents lethal ventricular tachycardia (VT) and pathological left ventricular (LV) remodeling and improves cardiac function in a mouse model of post-myocardial infarction (MI) [1]. We agree with all observations that have been made to show the acute and chronic effects of dantrolene in a chronic ischemic heart disease model. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - July 5, 2023 Category: Cytology Authors: Shigeki Kobayashi, Takeshi Yamamoto, Masafumi Yano Tags: Letter to the editor Source Type: research

Integrated metabolic and epigenetic mechanisms in cardiomyocyte proliferation
Heart disease continues to be the leading cause of mortality worldwide, primarily attributed to the restricted regenerative potential of the adult human heart following injury. In contrast to their adult counterparts, many neonatal mammals can spontaneously regenerate their myocardium in the first few days of life via extensive proliferation of the pre-existing cardiomyocytes. Reasons for the decline in regenerative capacity during postnatal development, and how to control it, remain largely unexplored. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - June 16, 2023 Category: Cytology Authors: Liying Huang, Qiyuan Wang, Shanshan Gu, Nan Cao Tags: Review article Source Type: research

Top-down proteomics of myosin light chain isoforms define chamber-specific expression in the human heart
Myosin functions as the “molecular motor” of the sarcomere and generates the contractile force necessary for cardiac muscle contraction. Myosin light chains 1 and 2 (MLC-1 and -2) play important functional roles in regulating the structure of the hexameric myosin molecule. Each of these light chains has an ‘atrial’ and ‘ventricular’ isoform, so called because they are believed to exhibit chamber-restricted expression in the heart. However, recently the chamber-specific expression of MLC isoforms in the human heart has been questioned. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - June 14, 2023 Category: Cytology Authors: Elizabeth F. Bayne, Kalina J. Rossler, Zachery R. Gregorich, Timothy J. Aballo, David S. Roberts, Emily A. Chapman, Wei Guo, Sean P. Palecek, J. Carter Ralphe, Timothy J. Kamp, Ying Ge Source Type: research

Ythdf2 regulates cardiac remodeling through its mRNA target transcripts
m6A mRNA methylation controls cardiomyocyte function and increased overall m6A levels are a stereotyping finding in heart failure independent of the underlying etiology. However, it is largely unknown how the information is read by m6A reader proteins in heart failure. Here we show that the m6A reader protein Ythdf2 controls cardiac function and identified a novel mechanism how reader proteins control gene expression and cardiac function. Deletion of Ythdf2 in cardiomyocytes in vivo leads to mild cardiac hypertrophy, reduced heart function, and increased fibrosis during pressure overload as well as during aging. (Source: J...
Source: Journal of Molecular and Cellular Cardiology - June 11, 2023 Category: Cytology Authors: V. Kmietczyk, J. Oelschl äger, P. Gupta, E. Varma, S. Hartl, J. Furkel, M. Konstandin, A. Marx, Z. Loewenthal, V. Kamuf-Schenk, L. Jürgensen, C. Stroh, A. Gorska, A. Martin-Garrido, J. Heineke, T. Jakobi, N. Frey, M. Völkers Source Type: research

RyR2 inhibition with dantrolene is antiarrhythmic, prevents further pathological remodeling, and improves cardiac function in chronic ischemic heart disease
Diastolic Ca2+ leak due to cardiac ryanodine receptor (RyR2) hyperactivity has been widely documented in chronic ischemic heart disease (CIHD) and may contribute to ventricular tachycardia (VT) risk and progressive left-ventricular (LV) remodeling. Here we test the hypothesis that targeting RyR2 hyperactivity can suppress VT inducibility and progressive heart failure in CIHD by the RyR2 inhibitor dantrolene. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - June 5, 2023 Category: Cytology Authors: Jeffrey Schmeckpeper, Kyungsoo Kim, Sharon A. George, Dan Blackwell, Jaclyn A. Brennan, Igor R. Efimov, Bjorn C. Knollmann Source Type: research

Prenatal dexamethasone exposure impaired vascular reactivity in adult male offspring cerebral arteries
Cerebrovascular disease is one of the leading causes of death worldwide. Middle cerebral artery (MCA) is the largest and most complex of cerebral arteries. The prenatal period is a critical time for development, which largely determines lifelong health. Clinically, glucocorticoids (GCs) administration to accelerate preterm fetal lung maturation has become standard practice. Prenatal GCs administration increases cardiovascular risks in offspring, but little is known regarding the side effects on offspring MCA function. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - June 2, 2023 Category: Cytology Authors: Jiahui Lei, Meng Zhao, Fengying Deng, Ting Xu, Bingyu Ji, Xietong Wang, Meihua Zhang, Miao Sun, Qinqin Gao Source Type: research

Maresin-1 protects against pulmonary arterial hypertension by improving mitochondrial homeostasis through ALXR/HSP90 α axis
Pulmonary arterial hypertension (PAH) is a progressive and lethal disease characterized by continuous proliferation of pulmonary arterial smooth muscle cell (PASMCs) and increased pulmonary vascular remodeling. Maresin-1 (MaR1) is a member of pro-resolving lipid mediators and exhibits protective effects on various inflammation-related diseases. Here we aimed to study the role of MaR1 in the development and progression of PAH and to explore the underlying mechanisms. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - May 25, 2023 Category: Cytology Authors: Min Liu, Huixiang He, Fenling Fan, Lejia Qiu, Feng Zheng, Youfei Guan, Guangrui Yang, Lihong Chen Source Type: research

Suppression of myeloid YAP antagonizes adverse cardiac remodeling during pressure overload stress
Inflammation is an integral component of cardiovascular disease and is thought to contribute to cardiac dysfunction and heart failure. While ischemia-induced inflammation has been extensively studied in the heart, relatively less is known regarding cardiac inflammation during non-ischemic stress. Recent work has implicated a role for Yes-associated protein (YAP) in modulating inflammation in response to ischemic injury; however, whether YAP influences inflammation in the heart during non-ischemic stress is not described. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - May 24, 2023 Category: Cytology Authors: Jamie Francisco, Jin Guan, Yu Zhang, Yasuki Nakada, Satvik Mareedu, Eunah Sung, Che-Ming Hu, Shinichi Oka, Peiyong Zhai, Junichi Sadoshima, Dominic P. Del Re Source Type: research

Absence (of the uniporter) makes the heart grow fonder: The cardiac response to injury adapts after prolonged EMRE inhibition
More than a decade after identifying the molecular components of the mitochondrial calcium uniporter, the main channel responsible for rapid mitochondrial Ca2+ uptake, questions remain regarding its modes of regulation during physiological and pathological stress. The uniporter complex comprises the pore-forming MCU subunit, targeting protein EMRE, gate-keeping proteins MICU 1, 2, and 3, and inhibitory subunit MCUB [1]. Maximal inhibition of rapid mitochondrial Ca2+ uptake can be obtained by genetic deletion of MCU, which prevents expression of the pore, or EMRE, which prevents accurate membrane targeting and assembly of M...
Source: Journal of Molecular and Cellular Cardiology - May 24, 2023 Category: Cytology Authors: Enrique Balderas, Dipayan Chaudhuri Source Type: research

Distinct effects of cardiac mitochondrial calcium uniporter inactivation via EMRE deletion in the short and long term
Transport of Ca2+ into mitochondria is thought to stimulate the production of ATP, a critical process in the heart's fight or flight response, but excess Ca2+ can trigger cell death. The mitochondrial Ca2+ uniporter complex is the primary route of Ca2+ transport into mitochondria, in which the channel-forming protein MCU and the regulatory protein EMRE are essential for activity. In previous studies, chronic Mcu or Emre deletion differ from acute cardiac Mcu deletion in response to adrenergic stimulation and ischemia/reperfusion (I/R) injury, despite equivalent inactivation of rapid mitochondrial Ca2+ uptake. (Source: Jour...
Source: Journal of Molecular and Cellular Cardiology - May 23, 2023 Category: Cytology Authors: Hector Chapoy Villanueva, Jae Hwi Sung, Jackie A. Stevens, Michael J. Zhang, Peyton M. Nelson, Saahiti Denduluri, Feng Feng, Timothy D. O'Connell, DeWayne Townsend, Julia C. Liu Source Type: research

Prediction of Kv11.1 potassium channel PAS-domain variants trafficking via machine learning
Congenital long QT syndrome (LQTS) is characterized by a prolonged QT-interval on an electrocardiogram (ECG). An abnormal prolongation in the QT-interval increases the risk for fatal arrhythmias. Genetic variants in several different cardiac ion channel genes, including KCNH2, are known to cause LQTS. Here, we evaluated whether structure-based molecular dynamics (MD) simulations and machine learning (ML) could improve the identification of missense variants in LQTS-linked genes. To do this, we investigated KCNH2 missense variants in the Kv11.1 channel protein shown to have wild type (WT) like or class II (trafficking-defic...
Source: Journal of Molecular and Cellular Cardiology - May 13, 2023 Category: Cytology Authors: Xuan Fang, Kalyan Immadisetty, Geraldine San Ramon, Cassandra M. Hartle, Thomas P. McCoy, Regeneron Genetics Center, Tooraj Mirshahi, Brian P. Delisle, Peter M. Kekenes-Huskey Source Type: research

NLRP3 inflammasome-driven IL-1 β and IL-18 contribute to lipopolysaccharide-induced septic cardiomyopathy
Sepsis is a life-threatening syndrome, and its associated mortality is increased when cardiac dysfunction and damage (septic cardiomyopathy [SCM]) occur. Although inflammation is involved in the pathophysiology of SCM, the mechanism of how inflammation induces SCM in vivo has remained obscure. NLRP3 inflammasome is a critical component of the innate immune system that activates caspase-1 (Casp1) and causes the maturation of IL-1 β and IL-18 as well as the processing of gasdermin D (GSDMD). Here, we investigated the role of the NLRP3 inflammasome in a murine model of lipopolysaccharide (LPS)-induced SCM. (Source: Journal o...
Source: Journal of Molecular and Cellular Cardiology - May 10, 2023 Category: Cytology Authors: Kenta Fujimura, Tadayoshi Karasawa, Takanori Komada, Naoya Yamada, Yoshiko Mizushina, Chintogtokh Baatarjav, Takayoshi Matsumura, Kinya Otsu, Norihiko Takeda, Hiroaki Mizukami, Kazuomi Kario, Masafumi Takahashi Source Type: research

Cardiac protein kinase D1 ablation alters the myocytes β-adrenergic response
β-adrenergic (β-AR) signaling is essential for the adaptation of the heart to exercise and stress. Chronic stress leads to the activation of Ca2+/calmodulin-dependent kinase II (CaMKII) and protein kinase D (PKD). Unlike CaMKII, the effects of PKD on excitation-contraction coupling (ECC) remain un clear. To elucidate the mechanisms of PKD-dependent ECC regulation, we used hearts from cardiac-specific PKD1 knockout (PKD1 cKO) mice and wild-type (WT) littermates. We measured calcium transients (CaT), Ca2+ sparks, contraction and L-type Ca2+ current in paced cardiomyocytes under acute β-AR stim ulation with isoproterenol (...
Source: Journal of Molecular and Cellular Cardiology - May 4, 2023 Category: Cytology Authors: Juliana Mira Hernandez, Christopher Y. Ko, Avery R. Mandel, Erin Y. Shen, Sonya Baidar, Ashley R. Christensen, Kim Hellgren, Stefano Morotti, Jody L. Martin, Bence Hegyi, Julie Bossuyt, Donald M. Bers Source Type: research

Comparing the effects of chemical Ca2+ dyes and R-GECO on contractility and Ca2+ transients in adult and human iPSC cardiomyocytes
We compared commonly used BAPTA-derived chemical Ca2+ dyes (fura2, Fluo-4, and Rhod-2) with a newer genetically encoded indicator (R-GECO) in single cell models of the heart. We assessed their performance and effects on cardiomyocyte contractility, determining fluorescent signal-to-noise ratios and sarcomere shortening in primary ventricular myocytes from adult mouse and guinea pig, and in human iPSC-derived cardiomyocytes. Chemical Ca2+ dyes displayed dose-dependent contractile impairment in all cell types, and we observed a negative correlation between contraction and fluorescence signal-to-noise ratio, particularly for ...
Source: Journal of Molecular and Cellular Cardiology - April 29, 2023 Category: Cytology Authors: Paul Robinson, Alexander J. Sparrow, Yiangos Psaras, Violetta Steeples, Jillian Simon, Connor N. Broyles, Yu-Fen Chang, Frances A. Brook, Ying-Jie Wang, Andrew Blease, Xiaoyu Zhang, Yama A. Abassi, Michael A. Geeves, Christopher N. Toepfer, Hugh Watkins, Source Type: research