OxLDL-mediated immunologic memory in endothelial cells
Trained innate immunity describes the metabolic reprogramming and long-term proinflammatory activation of innate immune cells in response to different pathogen or damage associated molecular patterns, such as oxidized low-density lipoprotein (oxLDL). Here, we have investigated whether the regulatory networks of trained innate immunity also control endothelial cell activation following oxLDL treatment. Human aortic endothelial cells (HAECs) were primed with oxLDL for 24  h. After a resting time of 4 days, cells were restimulated with the TLR2-agonist PAM3cys4. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - July 26, 2020 Category: Cytology Authors: Yahya Sohrabi, Sina M.M. Lagache, Vivienne C. Voges, Dilvin Semo, Glenn Sonntag, Irene Hanemann, Florian Kahles, Johannes Waltenberger, Hannes M. Findeisen Source Type: research

Mcl-1-mediated mitochondrial fission protects against stress but impairs cardiac adaptation to exercise
Myeloid cell leukemia-1 (Mcl-1) is a structurally and functionally unique anti-apoptotic Bcl-2 protein. While elevated levels of Mcl-1 contribute to tumor cell survival and drug resistance, loss of Mcl-1 in cardiac myocytes leads to rapid mitochondrial dysfunction and heart failure development. Although Mcl-1 is an anti-apoptotic protein, previous studies indicate that its functions extend beyond regulating apoptosis. Mcl-1 is localized to both the mitochondrial outer membrane and matrix. Here, we have identified that Mcl-1 in the outer mitochondrial membrane mediates mitochondrial fission, which is independent of its anti...
Source: Journal of Molecular and Cellular Cardiology - July 25, 2020 Category: Cytology Authors: Alexandra G. Moyzis, Navraj S. Lally, Wenjing Liang, Leonardo J. Leon, Rita H. Najor, Amabel M. Orogo, Åsa B. Gustafsson Source Type: research

Systolic overload-induced pulmonary inflammation, fibrosis, oxidative stress and heart failure progression through interleukin-1 β
Chronic heart failure is associated with increased interleukin-1 β (IL-1β), leukocyte infiltration, and fibrosis in the heart and lungs. Here we further studied the role of IL-1β in the transition from left heart failure to pulmonary hypertension and right ventricular hypertrophy in mice with existing left heart failure produced by transverse aortic constricti on. We demonstrated that transverse aortic constriction-induced heart failure was associated with increased lung inflammation and cleaved IL-1β, and inhibition of IL-1β signaling using blocking antibodies of clone: B122 effectively attenuated...
Source: Journal of Molecular and Cellular Cardiology - July 23, 2020 Category: Cytology Authors: Linlin Shang, Wenhui Yue, Dongzhi Wang, Xinyu Weng, Michael E. Hall, Yawei Xu, Mingxiao Hou, Yingjie Chen Source Type: research

Cardiomyocyte cell cycling, maturation, and growth by multinucleation in postnatal swine
Rodent cardiomyocytes (CM) undergo mitotic arrest and decline of mononucleated-diploid population post-birth, which are implicated in neonatal loss of heart regenerative potential. However, the dynamics of postnatal CM maturation are largely unknown in swine, despite a similar neonatal cardiac regenerative capacity as rodents. Here, we provide a comprehensive analysis of postnatal cardiac maturation in swine, including CM cell cycling, multinucleation and hypertrophic growth, as well as non-CM cardiac factors such as extracellular matrix (ECM), immune cells, capillaries, and neurons. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - July 22, 2020 Category: Cytology Authors: Nivedhitha Velayutham, Christina M. Alfieri, Emma J. Agnew, Kyle W. Riggs, R. Scott Baker, Sithara Raju Ponny, Farhan Zafar, Katherine E. Yutzey Source Type: research

Acute effects of alcohol on cardiac electrophysiology and arrhythmogenesis: Insights from multiscale in silico analyses
Acute excessive ethyl alcohol (ethanol) consumption alters cardiac electrophysiology and can evoke cardiac arrhythmias, e.g., in ‘holiday heart syndrome’. Ethanol acutely modulates numerous targets in cardiomyocytes, including ion channels, calcium-handling proteins and gap junctions. However, the mechanisms underlying ethanol-induced arrhythmogenesis remain incompletely understood and difficult to study experimentally du e to the multiple electrophysiological targets involved and their potential interactions with preexisting electrophysiological or structural substrates. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - July 22, 2020 Category: Cytology Authors: Henry Sutanto, Matthijs J.M. Cluitmans, Dobromir Dobrev, Paul G.A. Volders, Mark éta Bébarová, Jordi Heijman Source Type: research

Using “old” medications to fight new COVID-19: Re-purposing with a purpose
When the COVID-19 pandemic first emerged at the end of 2019, there were many speculations about the potential impact and course of progression, but none would have imagined the speed and the scale of its spread and devastation to people's lives and livelihood across the global [1,2]. Despite the unprecedented efforts and rapid scientific progress in the discovery of the cellular and molecular details for the pathogenesis of COVID-19 as a result of SARS-COV2 infection, there are still no specific new therapies that have been approved to either prevent or treat COVID19 in clinics [1,2]. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - July 17, 2020 Category: Cytology Authors: Yibin Wang, Roger Foo, Thomas Thum Tags: Letter to the editor Source Type: research

Coagulopathy in COVID-19: Focus on vascular thrombotic events
SARS-CoV-2 causes a phenotype of pneumonia with diverse manifestation, which is termed as coronavirus disease 2019 (COVID-19). An impressive high transmission rate allows COVID-19 conferring enormous challenge for clinicians worldwide, and developing to a pandemic level. Combined with a series of complications, a part of COVID-19 patients progress into severe cases, which critically contributes to the risk of fatality. To date, coagulopathy has been found as a prominent feature of COVID-19 and severe coagulation dysfunction may be associated with poor prognosis. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - July 15, 2020 Category: Cytology Authors: Wei Shi, Jiagao Lv, Li Lin Source Type: research

Simultaneous quantitative assessment of two distinct cell lineages with a nuclear-localized dual genetic reporter
Genetic lineage tracing has been widely used for studying in vivo cell fate plasticity during embryogenesis, tissue homeostasis, and disease development. Recent applications with multiple site-specific recombinases have been used in complex and sophisticated genetic fate mapping studies. However, the previous multicolor reporters for dual recombinases had limitations of precise in situ quantification of cell number, which is mainly due to the intermingling of cells in condensed tissues. Here, we generated a dual recombinase-mediated nuclear-localized GFP and tdTomato reporter line, which enables clear, simultaneous quantif...
Source: Journal of Molecular and Cellular Cardiology - July 12, 2020 Category: Cytology Authors: Muxue Tang, Kuo Liu, Hengwei Jin, Yan Li, Shaohua Zhang, Xiuxiu Liu, Ximeng Han, Maoying Han, Zhenqian Zhang, Bin Zhou Source Type: research

Pleiotropic cardiac functions controlled by ischemia-induced lncRNA H19
Myocardial ischemia induces a multifaceted remodeling process in the heart. Novel therapeutic entry points to counteract maladaptive signalling include the modulation of non-coding RNA molecules such as long non-coding RNA (lncRNA). We here questioned if the lncRNA candidate H19 exhibits regulatory potential in the setting of myocardial infarction. Initial profiling of H19 expression revealed a dynamic expression profile of H19 with upregulation in the acute phase after murine cardiac ischemia. In vitro, we found that oxygen deficiency leads to H19 upregulation in several cardiac cell types. (Source: Journal of Molecular a...
Source: Journal of Molecular and Cellular Cardiology - July 7, 2020 Category: Cytology Authors: Lisa Hobu ß, Ariana Foinquinos, Mira Jung, Franziska Kenneweg, Ke Xiao, Yong Wang, Karina Zimmer, Janet Remke, Annette Just, Juliette Nowak, Arne Schmidt, Andreas Pich, Stephane Mazlan, Stella M. Reamon-Buettner, Gustavo Campos Ramos, Stefan Frantz, Jani Source Type: research

Misoprostol attenuates neonatal cardiomyocyte proliferation through Bnip3, perinuclear calcium signaling, and inhibition of glycolysis
Systemic hypoxia resulting from preterm birth, altered lung development, and cyanotic congenital heart disease is known to impede the regulatory and developmental pathways in the neonatal heart. While the molecular mechanisms are still unknown, hypoxia induces aberrant cardiomyocyte proliferation, which may be initially adaptive, but can ultimately program the heart to fail in early life. Recent evidence suggests that the prostaglandin E1 analogue, misoprostol, is cytoprotective in the hypoxia-exposed neonatal heart by impacting alternative splicing of the Bcl-2 family member Bnip3, resulting in the generation of a variant...
Source: Journal of Molecular and Cellular Cardiology - July 4, 2020 Category: Cytology Authors: Matthew D. Martens, Jared T. Field, Nivedita Seshadri, Chelsea Day, Donald Chapman, Richard Keijzer, Christine A. Doucette, Grant M. Hatch, Adrian R. West, Tammy L. Ivanco, Joseph W. Gordon Source Type: research

Circulating microRNAs differentiate Kawasaki Disease from infectious febrile illnesses in childhood
Kawasaki Disease (KD) is an acute vasculitis of unknown etiology in children that can lead to coronary artery lesions (CAL) in 25% of untreated patients. There is currently no diagnostic test for KD, and the clinical presentation is often difficult to differentiate from other febrile childhood illnesses. Circulating microRNAs (miRNAs) are small noncoding RNA molecules that control gene expression by inducing transcript degradation or by blocking translation. We hypothesize that the expression of circulating miRNAs will differentiate KD from non-KD febrile illnesses in children. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - July 4, 2020 Category: Cytology Authors: Pei-Ni Jone, Armin Korst, Anis Karimpour-Fard, Thomas Thomas, Samuel R. Dominguez, Heather Heizer, Marsha S. Anderson, Mary P. Glode, Carmen C. Sucharov, Shelley D. Miyamoto Source Type: research

Unsolved mysteries and controversies of mitochondria in the heart – A Virtual Special Issue in JMCC: Part III
Five years ago, JMCC published a special issue that reviewed a number of exciting advancements in basic and translational research of mitochondrial biology [1]. It seemed that, with these breakthrough discoveries, many mysteries surrounding mitochondrial function and regulation were solved or could be solved by now. Undoubtedly, tremendous progress has been made during the past few years from widespread cutting-edge investigations on this research area; nevertheless, mysteries and controversies remain in several critical questions. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - June 27, 2020 Category: Cytology Authors: Wang Wang, Shey-Shing Sheu Source Type: research

Enhancing fatty acid oxidation negatively regulates PPARs signaling in the heart
In this study, increasing FAO by genetic deletion of acetyl-CoA carboxylase 2 (ACC2) did not induce cardiac dysfunction after 16  weeks of high fat diet (HFD) feeding. This suggests that increasing FAO, per se, does not cause metabolic cardiomyopathy in obese mice. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - June 24, 2020 Category: Cytology Authors: ZhengLong Liu, Jeffrey Ding, Timothy S. McMillen, Outi Villet, Rong Tian, Dan Shao Source Type: research

Exogenous IL-4 shuts off pro-inflammation in neutrophils while stimulating anti-inflammation in macrophages to induce neutrophil phagocytosis following myocardial infarction
Macrophages and neutrophils are primary leukocytes involved in the inflammatory response to myocardial infarction (MI). While interleukin (IL)-4 is an in vitro anti-inflammatory stimulus, the MI myocardium does not express a considerable amount of IL-4 but does express IL4 receptors. We hypothesized that continuous exogenous IL-4 infusion starting 24  h after MI would promote a polarization switch in inflammatory cells towards a reparative phenotype. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - June 20, 2020 Category: Cytology Authors: Michael J. Daseke, Mavis A.A. Tenkorang-Impraim, Yonggang Ma, Upendra Chalise, Shelby R. Konfrst, Michael R. Garrett, Kristine Y. DeLeon-Pennell, Merry L. Lindsey Source Type: research

Apelin-potential therapy for COVID-19?
We believe that, in parallel to the attempts for direct blockade of the SARS-CoV-2 penetration into host cell and repurposing drugs, finding new therapeutic strategies for patients with lung injury or cardiovascular complications/coagulopathies associated with COVID-19 should be paid particular attention. Apelin or its receptor agonists are of great potential treatment for COVID-19 through suppressing angiotensin-converting enzyme (ACE) and angiotensin II (Ang-II) production, as well as, down-regulating angiotensin receptor 1 (AT1R) and ACE2 up-regulation. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - June 17, 2020 Category: Cytology Authors: Seyed Soheil Saeedi Saravi, J ürg H. Beer Tags: Short communication Source Type: research

CYLD exaggerates pressure overload-induced cardiomyopathy via suppressing autolysosome efflux in cardiomyocytes
Deubiquitinating enzymes (DUBs) appear to be a new class of regulators of cardiac homeostasis and disease. However, DUB-mediated signaling in the heart is not well understood. Herein we report a novel mechanism by which cylindromatosis (CYLD), a DUB mediates cardiac pathological remodeling and dysfunction. Cardiomyocyte-restricted (CR) overexpression of CYLD (CR-CYLD) did not cause gross health issues and hardly affected cardiac function up to age of one year in both female and male mice at physiological conditions. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - June 14, 2020 Category: Cytology Authors: Lei Qi, Huimei Zang, Weiwei Wu, Prakash Nagarkatti, Mitzi Nagarkatti, Qinghang Liu, Jeffrey Robbins, Xuejun Wang, Taixing Cui Source Type: research

POPDC2 a novel susceptibility gene for conduction disorders
Despite recent progress in the understanding of cardiac ion channel function and its role in inherited forms of ventricular arrhythmias, the molecular basis of cardiac conduction disorders often remains unresolved. We aimed to elucidate the genetic background of familial atrioventricular block (AVB) using a whole exome sequencing (WES) approach. In monozygotic twins with a third-degree AVB and in another, unrelated family with first-degree AVB, we identified a heterozygous nonsense mutation in the POPDC2 gene causing a premature stop at position 188 (POPDC2W188 ⁎), deleting parts of its cAMP binding-domain. (Source: Jour...
Source: Journal of Molecular and Cellular Cardiology - June 11, 2020 Category: Cytology Authors: Susanne Rinn é, Beatriz Ortiz-Bonnin, Birgit Stallmeyer, Aytug K. Kiper, Lisa Fortmüller, Roland F.R. Schindler, Ursula Herbort-Brand, Nashitha S. Kabir, Sven Dittmann, Corinna Friedrich, Sven Zumhagen, Francesca Gualandi, Rita Selvatici, Claudio Rapezz Source Type: research

Global analysis of histone modifications and long-range chromatin interactions revealed the differential cistrome changes and novel transcriptional players in human dilated cardiomyopathy
Acetylation and methylation of histones alter the chromatin structure and accessibility that affect transcriptional regulators binding to enhancers and promoters. The binding of transcriptional regulators enables the interaction between enhancers and promoters, thus affecting gene expression. However, our knowledge of these epigenetic alternations in patients with heart failure remains limited. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - June 10, 2020 Category: Cytology Authors: Chia-Feng Liu, Armen Abnousi, Peter Bazeley, Ying Ni, Michael Morley, Christine S. Moravec, Ming Hu, W.H. Wilson Tang Source Type: research

Isogenic models of hypertrophic cardiomyopathy unveil differential phenotypes and mechanism-driven therapeutics
Hypertrophic cardiomyopathy (HCM) is a prevalent and complex cardiovascular condition. Despite being strongly associated with genetic alterations, wide variation of disease penetrance, expressivity and hallmarks of progression complicate treatment. We aimed to characterize different human isogenic cellular models of HCM bearing patient-relevant mutations to clarify genetic causation and disease mechanisms, hence facilitating the development of effective therapeutics. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - June 9, 2020 Category: Cytology Authors: Jamie R. Bhagwan, Diogo Mosqueira, Karolina Chairez-Cantu, Ingra Mannhardt, Sara E. Bodbin, Mine Bakar, James G.W. Smith, Chris Denning Source Type: research

Type 2 innate lymphoid cells regulation by regulatory T cells attenuates atherosclerosis
Regulatory T cells (Tregs) have been shown to attenuate the development and progression of atherosclerosis; however, the exact mechanism is still unclear. In our study, Tregs were adoptively transferred into ApoE −/− mice, and type 2 innate lymphoid cells (ILC2s) were expanded by the IL-2/Jes6-1 complex or depleted by anti-CD90.2 mAb in ApoE−/-Rag1−/− mice to study their effects on atherosclerosis. Then, Tregs were cocultured with ILC2s in vitro to analyze ILC2s number and IL-13 production. In vivo , ApoE−/-Rag1−/− mice were treated with activated Tregs with or without anti-C...
Source: Journal of Molecular and Cellular Cardiology - June 8, 2020 Category: Cytology Authors: Xiaonan Gao, Jibin Lin, Yuqi Zheng, Shangwei Liu, Chengxing Liu, Tianxiao Liu, Boyuan Wang, Shaolin He, Dazhu Li Source Type: research

Cardiac injuries in coronavirus disease 2019 (COVID-19)
As the coronavirus disease 2019 (COVID-19) epidemic worsens, this global pandemic is impacting more than 200 countries/regions and more than 4,500,000 confirmed cases worldwide. COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which might attack not only the respiratory system, but also the other important organs, including the heart. It was reported that COVID-19 patients with a past history of cardiovascular diseases would have a higher mortality. Meanwhile, elevated troponin levels were frequently observed in COVID-19 cases. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - June 8, 2020 Category: Cytology Authors: Chen Chen, Huihui Li, Weijian Hang, Dao Wen Wang Tags: Short communication Source Type: research

Glucose fluctuations promote vascular BK channels dysfunction via PKC α/NF-κB/MuRF1 signaling
Glucose fluctuations may contribute to large conductance calcium activated potassium (BK) channel dysfunction. However, the underlying mechanisms remain elusive. The aim of this study was to investigate the molecular mechanisms involved in BK channel dysfunction as a result of glucose fluctuations. A rat diabetic model was established through the injection of streptozotocin. Glucose fluctuations in diabetic rats were induced via consumption and starvation. Rat coronary arteries were isolated and coronary vascular tensions were measured after three weeks. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - June 5, 2020 Category: Cytology Authors: Zhen-Ye Zhang, Ling-Ling Qian, Ning Wang, Ling-Feng Miao, Xin Ma, Shi-Peng Dang, Ying Wu, Xiao-Yu Liu, Xiao-Yan Li, Qiang Chai, Min Pan, Fu Yi, Tian-You Ling, Ru-Xing Wang Source Type: research

Identifying temporal molecular signatures underlying cardiovascular diseases: A data science platform
During cardiovascular disease progression, molecular systems of myocardium (e.g., a proteome) undergo diverse and distinct changes. Dynamic, temporally-regulated alterations of individual molecules underlie the collective response of the heart to pathological drivers and the ultimate development of pathogenesis. Advances in high-throughput omics technologies have enabled cost-effective, temporal profiling of targeted systems in animal models of human disease. However, computational analysis of temporal patterns from omics data remains challenging. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - June 3, 2020 Category: Cytology Authors: Neo Christopher Chung, Howard Choi, Ding Wang, Bilal Mirza, Alexander R. Pelletier, Dibakar Sigdel, Wei Wang, Peipei Ping Source Type: research

Stephen M. Schwartz (1942 –2020)
On March 17, 2020, devastating news hit the campus of University of Washington: Dr. Steve Schwartz, Professor of Pathology, had succumbed to complications of COVID-19. The school lost a distinguished faculty member of half a century, the vascular biology community lost a strong leader and the entire scientific world lost a larger than life scientist. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - June 2, 2020 Category: Cytology Tags: Editorial Source Type: research

Cyclic AMP represses pathological MEF2 activation by myocyte-specific hypo-phosphorylation of HDAC5
Class IIa histone deacetylases (HDACs) critically regulate cardiac function through the repression of the activity of myocyte enhancer factor 2 (MEF2)-dependent gene programs. Protein kinase D (PKD) and Ca2+/Calmodulin-dependent kinase II (CaMKII) activate MEF2 by phosphorylating distinct HDAC isoforms and thereby creating 14 –3-3 binding sites for nucleo-cytoplasmic shuttling. Recently, it has been shown that this process is counteracted by cyclic AMP (cAMP)-dependent signaling. Here, we investigated the specific mechanisms of how cAMP-dependent signaling regulates distinct HDAC isoforms and determined their relativ...
Source: Journal of Molecular and Cellular Cardiology - May 30, 2020 Category: Cytology Authors: Tao He, Jiale Huang, Lan Chen, Gang Han, David Stanmore, Jutta Krebs-Haupenthal, Metin Avkiran, Marco Hagenm üller, Johannes Backs Source Type: research

Unsolved mysteries and controversies of mitochondria in the heart – A virtual special issue in JMCC: Part II
Five years ago, JMCC published a special issue that reviewed a number of exciting advancements in basic and translational research of mitochondrial biology [1]. It seemed that, with these breakthrough discoveries, many mysteries surrounding mitochondrial function and regulation were solved or could be solved by now. Undoubtedly, tremendous progress has been made during the past few years from widespread cutting-edge investigations on this research area; nevertheless, mysteries and controversies remain in several critical questions. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - May 26, 2020 Category: Cytology Authors: Wang Wang, Shey-Shing Sheu Source Type: research

Identifying modifier genes for hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy (HCM) severity greatly varies among patients even with the same HCM gene mutations. This variation is largely regulated by modifier gene(s), which, however, remain largely unknown. The current study is aimed to identify modifier genes using BXD strains, a large murine genetic reference population (GRP) derived from crosses between C57BL/6  J (B6) and D2 DBA/2 J (D2) mice. D2 mice is a natural model that carry the genetic basis and phenotypes of HCM. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - May 25, 2020 Category: Cytology Authors: Yuanjian Chen, Fuyi Xu, Undral Munkhsaikhan, Charlie Boyle, Theresa Borcky, Wenyuan Zhao, Enkhsaikhan Purevjav, Jeffrey A. Towbin, Fang Liao, Robert W. Williams, Syamal K. Bhattacharya, Lu Lu, Yao Sun Source Type: research

Metformin protects against ischaemic myocardial injury by alleviating autophagy-ROS-NLRP3-mediated inflammatory response in macrophages
Myocardial ischaemia is usually accompanied by inflammatory response which plays a critical role in the myocardial healing and scar formation, while persistent inflammatory response contributes greatly to the myocardial remodeling and consequent heart failure. Metformin (Met), a widely used hypoglycemic drug, has increasingly been shown to exert remarkable cardioprotective effect on ischaemic myocardial injury such as acute myocardial infarction (AMI). However, the underlying mechanisms are still far from being fully understood. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - May 25, 2020 Category: Cytology Authors: Qin Fei, Heng Ma, Jiang Zou, Wenmei Wang, Lili Zhu, Huafei Deng, Meng Meng, Sipin Tan, Huali Zhang, Xianzhong Xiao, Nian Wang, Kangkai Wang Source Type: research

ATP synthase c-subunit ring as the channel of mitochondrial permeability transition: Regulator of metabolism in development and degeneration
The mitochondrial permeability transition pore (mPTP) or mitochondrial megachannel is arguably one of the most mysterious phenomena in biology today. mPTP has been at the center of ongoing extensive scientific research for the last several decades. In this review we will discuss recent advances in the field that enhance our understanding of the molecular composition of mPTP, its regulatory mechanisms and its pathophysiological role. We will describe our recent findings on the role of ATP synthase c-subunit ring as a central player in mitochondrial permeability transition and as an important metabolic regulator during devel...
Source: Journal of Molecular and Cellular Cardiology - May 23, 2020 Category: Cytology Authors: Nelli Mnatsakanyan, Elizabeth Ann Jonas Source Type: research

A 20/20 view of ANT function in mitochondrial biology and necrotic cell death
The adenosine nucleotide translocase (ANT) family of proteins are inner mitochondrial membrane proteins involved in energy homeostasis and cell death. The primary function of ANT proteins is to exchange cytosolic ADP with matrix ATP, facilitating the export of newly synthesized ATP to the cell while providing new ADP substrate to the mitochondria. As such, the ANT proteins are central to maintaining energy homeostasis in all eukaryotic cells. Evidence also suggests that the ANTs constitute a pore-forming component of the mitochondrial permeability transition pore (MPTP), a structure that forms in the inner mitochondrial me...
Source: Journal of Molecular and Cellular Cardiology - May 23, 2020 Category: Cytology Authors: Michael J. Bround, Donald M. Bers, Jeffery D. Molkentin Source Type: research

Molecular nature and regulation of the mitochondrial permeability transition pore(s), drug target(s) in cardioprotection
The mitochondrial permeability transition, an established mechanism for heart diseases, is a long-standing mystery of mitochondrial biology and a prime drug target for cardioprotection. Several hypotheses about its molecular nature have been put forward over the years, and the prevailing view is that permeabilization of the inner mitochondrial membrane follows opening of a high-conductance channel, the permeability transition pore, which is also called mitochondrial megachannel or multiconductance channel. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - May 23, 2020 Category: Cytology Authors: Michela Carraro, Andrea Carrer, Andrea Urbani, Paolo Bernardi Source Type: research

miR-374b-5p is increased in deep vein thrombosis and negatively targets IL-10
Deep venous thrombosis (DVT) is one of the most common venous thromboembolic (VTE) disorders and the third leading cardiovascular complication. Accumulating evidence has shown that decreased interleukin-10 (IL-10) was involved in DVT. However, the underlying molecular mechanisms are still largely unknown. Here, we proposed that the epigenetic modification of IL-10 at the post-transcriptional level may be a crucial trigger for IL-10 down-regulation in DVT. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - May 20, 2020 Category: Cytology Authors: Yunhong Zhang, Xiuming Miao, Zhen Zhang, Ran Wei, Shangwen Sun, Gang Liang, Huihan Li, Chu Chu, Lin Zhao, Xiaoxiao Zhu, Qiang Guo, Bin Wang, Xia Li Source Type: research

Microtubule polymerization state and clathrin-dependent internalization regulate dynamics of cardiac potassium channel
on channel trafficking powerfully influences cardiac electrical activity as it regulates the number of available channels at the plasma membrane. Studies have largely focused on identifying the molecular determinants of the trafficking of the atria-specific KV1.5 channel, the molecular basis of the ultra-rapid delayed rectifier current IKur. Besides, regulated KV1.5 channel recycling upon changes in homeostatic state and mechanical constraints in native cardiomyocytes has been well documented. Here, using cutting-edge imaging in live myocytes, we investigated the dynamics of this channel in the plasma membrane. (Source: Jo...
Source: Journal of Molecular and Cellular Cardiology - May 19, 2020 Category: Cytology Authors: Dario Melgari, Camille Barbier, Gilles Dilanian, Catherine R ücker-Martin, Nicolas Doisne, Alain Coulombe, Stéphane N. Hatem, Elise Balse Source Type: research

Nuclear-mitochondrial communication involving miR-181c plays an important role in cardiac dysfunction during obesity
In cardiomyocytes, there is microRNA (miR) in the mitochondria that originates from the nuclear genome and matures in the cytoplasm before translocating into the mitochondria. Overexpression of one such miR, miR-181c, can lead to heart failure by stimulating reactive oxygen species (ROS) production and increasing mitochondrial calcium level ([Ca2+]m). Mitochondrial calcium uptake 1 protein (MICU1), a regulatory protein in the mitochondrial calcium uniporter complex, plays an important role in regulating [Ca2+]m. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - May 19, 2020 Category: Cytology Authors: Barbara Roman, Pawandeep Kaur, Deepthi Ashok, Mark Kohr, Roopa Biswas, Brian O'Rourke, Charles Steenbergen, Samarjit Das Source Type: research

StatinImplications of the complex biology and micro-environment of cardiac sarcomeres in the use of high affinity troponin antibodies as serum biomarkers for cardiac disorders
Cardiac troponin I (cTnI), the inhibitory-unit, and cardiac troponin T (cTnT), the tropomyosin-binding unit together with the Ca-binding unit (cTnC) of the hetero-trimeric troponin complex signal activation of the sarcomeres of the adult cardiac myocyte. The unique structure and heart myocyte restricted expression of cTnI and cTnT led to their worldwide use as biomarkers for acute myocardial infarction (AMI) beginning more than 30  years ago. Over these years, high sensitivity antibodies (hs-cTnI and hs-cTnT) have been developed. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - May 18, 2020 Category: Cytology Authors: Christopher R. Solaro, R. John Solaro Source Type: research

A directed network analysis of the cardiome identifies molecular pathways contributing to the development of HFpEF
The metabolic syndrome and associated comorbidities, like diabetes, hypertension and obesity, have been implicated in the development of heart failure with preserved ejection fraction (HFpEF). The molecular mechanisms underlying the development of HFpEF remain to be elucidated. We developed a cardiome-directed network analysis and applied this to high throughput cardiac RNA-sequencing data from a well-established rat model of HFpEF, the obese and hypertensive ZSF1 rat. With this novel system biology approach, we explored the mechanisms underlying HFpEF. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - May 15, 2020 Category: Cytology Authors: Georg Summer, Annika R. Kuhn, Chantal Munts, Daniela Miranda-Silva, Adelino F. Leite-Moreira, Andr é P. Lourenço, Stephane Heymans, Inês Falcão-Pires, Marc van Bilsen Source Type: research

Remembering Stephen Schwartz
The field of vascular biology has suffered a tremendous loss with the passing of Dr. Stephen M. Schwartz, former Professor of Pathology at the University of Washington. He was one of the ‘founding fathers’ of the field and established a lasting legacy as one of the key architects of the North American Vascular Biology Organization (NAVBO). On a personal note, Steve was not only a treasured scientific colleague, but he was also a friend and mentor to me throughout my scientific c areer. As I grieve his loss, I have found some solace in the outpouring of messages of condolences, remembrances, profound respect and...
Source: Journal of Molecular and Cellular Cardiology - May 15, 2020 Category: Cytology Authors: Gary H. Gibbons Tags: Letter to the editor Source Type: research

p38 MAPK inhibition: A promising therapeutic approach for COVID-19
COVID-19, caused by the SARS-CoV-2 virus, is a major source of morbidity and mortality due to its inflammatory effects in the lungs and heart. The p38 MAPK pathway plays a crucial role in the release of pro-inflammatory cytokines such as IL-6 and has been implicated in acute lung injury and myocardial dysfunction. The overwhelming inflammatory response in COVID-19 infection may be caused by disproportionately upregulated p38 activity, explained by two mechanisms. First, angiotensin-converting enzyme 2 (ACE2) activity is lost during SARS-CoV-2 viral entry. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - May 15, 2020 Category: Cytology Authors: Joseph M. Grimes, Kevin V. Grimes Tags: Short communication Source Type: research

Contribution of the neuronal sodium channel NaV1.8 to sodium- and calcium-dependent cellular proarrhythmia
In myocardial pathology such as heart failure a late sodium current (INaL) augmentation is known to be involved in conditions of arrhythmogenesis. However, the underlying mechanisms of the INaL generation are not entirely understood. By now evidence is growing that non-cardiac sodium channel isoforms could also be involved in the INaL generation. The present study investigates the contribution of the neuronal sodium channel isoform NaV1.8 to arrhythmogenesis in a clearly-defined setting of enhanced INaL by using anemone toxin II (ATX-II) in the absence of structural heart disease. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - May 10, 2020 Category: Cytology Authors: Philipp Bengel, Shakil Ahmad, Petros Tirilomis, Maximilian Trum, Nataliya Dybkova, Stefan Wagner, Lars S. Maier, Gerd Hasenfu ß, Samuel Sossalla Source Type: research

Cardiolipin deficiency elevates susceptibility to a lipotoxic hypertrophic cardiomyopathy
Cardiolipin (CL) is a unique tetra-acyl phospholipid localized to the inner mitochondrial membrane and essential for normal respiratory function. It has been previously reported that the failing human heart and several rodent models of cardiac pathology have a selective loss of CL. A rare genetic disease, Barth syndrome (BTHS), is similarly characterized by a cardiomyopathy due to reduced levels of cardiolipin. A mouse model of cardiolipin deficiency was recently developed by knocking-down the cardiolipin biosynthetic enzyme tafazzin (TAZ KD). (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - May 10, 2020 Category: Cytology Authors: Laura K. Cole, Edgard M. Mejia, Genevieve C. Sparagna, Marilyne Vandel, Bo Xiang, Xianlin Han, Nikolaos Dedousis, Brett A. Kaufman, Vernon W. Dolinsky, Grant M. Hatch Source Type: research

Contribution of the neuronal sodium channel NaV1.8 to sodium and calcium-dependent cellular proarrhythmia
In myocardial pathology such as heart failure a late sodium current (INaL) augmentation is known to be involved in conditions of arrhythmogenesis. However, the underlying mechanisms of the INaL generation are not entirely understood. By now evidence is growing that non-cardiac sodium channel isoforms could also be involved in the INaL generation. The present study investigates the contribution of the neuronal sodium channel isoform NaV1.8 to arrhythmogenesis in a clearly-defined setting of enhanced INaL by using anemone toxin II (ATX-II) in the absence of structural heart disease. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - May 10, 2020 Category: Cytology Authors: Philipp Bengel, Shakil Ahmad, Petros Tirilomis, Maximilian Trum, Nataliya Dybkova, Stefan Wagner, Lars S. Maier, Gerd Hasenfuss, Samuel Sossalla Source Type: research

Identifying functional non-coding variants in APOA5/A4/C3/A1 gene cluster associated with coronary heart disease
In this study, a 2.7-kb length of the non-coding region between APOA1 and APOC3 was screened and five polymorphisms were investigated in the case –control study. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - May 10, 2020 Category: Cytology Authors: Guanglin Cui, Min Tian, Senlin Hu, Yan Wang, Dao Wen Wang Tags: Short communication Source Type: research

Is MCU dispensable for normal heart function?
The uptake of Ca2+ into mitochondria is thought to be an important signal communicating the need for increased energy production. However, dysregulated uptake leading to mitochondrial Ca2+ overload can trigger opening of the mitochondrial permeability transition pore and potentially cell death. Thus mitochondrial Ca2+ entry is regulated via the activity of a Ca2+-selective channel known as the mitochondrial calcium uniporter. The last decade has seen enormous momentum in the discovery of the molecular identities of the multiple proteins comprising the uniporter. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - May 7, 2020 Category: Cytology Authors: Julia C. Liu Source Type: research

Dexamethasone inhibits regeneration and causes ventricular aneurysm in the neonatal porcine heart after myocardial infarction
Recently, we demonstrated that the hearts of neonatal pigs (2-day old) have regenerative capacity, likely driven by cardiac myocyte division, but this potential is lost immediately after postnatal day 3. However, it is unknown if corticosteroid, a broad anti-inflammatory agent, will abrogate the regenerative capacity in the hearts of neonatal pigs. The aim of the current study is to evaluate the effect Dexamethasone (Dex), a broad anti-inflammatory agent, on heart regeneration, structure, and function of the neonatal pigs' post-myocardial infarction (MI). (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - May 5, 2020 Category: Cytology Authors: Zhonghao Tao, Szejie Loo, Liping Su, Desiree Abdurrachim, Janise Lalic, Teck Hock Lee, Xin Chen, Ru-San Tan, Jianyi Zhang, Lei Ye Source Type: research

Extracellular vesicular MicroRNA-27a* contributes to cardiac hypertrophy in chronic heart failure
Under stress, the heart undergoes extensive remodeling resulting in cardiac fibrosis and hypertrophy, ultimately contributing to chronic heart failure (CHF). Alterations in microRNA levels are associated with dysfunctional gene expression profiles involved in the pathogenesis of heart failure. We previously showed that myocardial infarction-induced microRNA-enriched extracellular vesicles (EVs) contribute to the reduction in antioxidant enzymes by targeting Nrf2 signaling in CHF. MicroRNA-27a (miRNA-27a) is the predominant microRNA contained in cardiac fibroblast-derived EVs contributing to oxidative stress along with hype...
Source: Journal of Molecular and Cellular Cardiology - May 3, 2020 Category: Cytology Authors: Changhai Tian, Guoku Hu, Lie Gao, Bryan T. Hackfort, Irving H. Zucker Source Type: research

A tribute to Stephen M. Schwartz, MD, PhD
The scientific world lost a larger-than-life figure with the passing of Stephen Schwartz, MD, PhD on March 17, 2020, at age 78 from complications of COVID-19 infection. I will say at the beginning that Steve was my mentor and a hugely influential person in my scientific development, so this tribute will be more personal than scholarly. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - April 30, 2020 Category: Cytology Authors: Chuck Murry Tags: Letter to the editor Source Type: research

SARS-CoV-2 receptor ACE2-dependent implications on the cardiovascular system: From basic science to clinical implications
The current COVID-19 pandemic started several months ago and is still exponentially growing in most parts of the world – this is the most recent and alarming update. COVID-19 requires the collaboration of nearly 200 countries to curb the spread of SARS-CoV-2 while gaining time to explore and improve treatment options especially for cardiovascular disease (CVD) and immunocompromised patients, who appear to be at hi gh-risk to die from cardiopulmonary failure. Currently unanswered questions are why elderly people, particularly those with pre-existing comorbidities seem to exhibit higher mortality rates after SARS-CoV-2...
Source: Journal of Molecular and Cellular Cardiology - April 30, 2020 Category: Cytology Authors: Sonja Gro ß, Christopher Jahn, Sarah Cushman, Christian Bär, Thomas Thum Source Type: research

Association with SERCA2a directs phospholamban trafficking to sarcoplasmic reticulum from a nuclear envelope pool
Phospholamban (PLB) stoichiometrically regulates the cardiac Ca2+ pump (SERCA2a) in the sarcoplasmic reticulum (SR); but in the nuclear envelope (NE) of cardiomyocytes (CMs), the PLB to SERCA2a molar ratio is higher, which highlights our poor understanding of how SR proteins distribute to their functional subcompartments. By tracking newly made PLB and SERCA2a in CMs, we will elucidate underlying cellular pathways responsible for their unique intracellular distributions. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - April 27, 2020 Category: Cytology Authors: Wenbo He, Dayang Huang, Shuai Guo, Danning Wang, Jin Guo, Steven E. Cala, Zhenhui Chen Source Type: research

The debate continues – What is the role of MCU and mitochondrial calcium uptake in the heart?
Since the initial identification of the mitochondrial calcium uniporter (MCU) in 2011, several studies employing genetic models have attempted to decipher the role of mitochondrial calcium uptake in cardiac physiology. Confounding results in various mutant mouse models have led to an ongoing debate regarding the function of MCU in the heart. In this review, we evaluate and discuss the totality of evidence for mitochondrial calcium uptake in the cardiac stress response. We highlight recent reports that implicate MCU in the control of homeostatic cardiac metabolism and function. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - April 27, 2020 Category: Cytology Authors: Joanne F. Garbincius, Timothy S. Luongo, John W. Elrod Source Type: research

Proteomic analysis of the cardiac myocyte secretome reveals extracellular protective functions for the ER stress response
In this study, the ER stressor thapsigargin (TG), which depletes ER calcium, induced death of cultured neonatal rat ventricular myocytes (NRVMs) in high media volume but fostered protection in low media volume. In contrast, another ER stressor, tunicamycin (TM), a protein glycosylation inhibitor, induced NRVM death in all media volumes, suggesting that protective proteins were secreted in response to TG but not TM. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - April 24, 2020 Category: Cytology Authors: Erik A. Blackwood, Donna J. Thuerauf, Miroslava Stastna, Haley Stephens, Zoe Sand, Amber Pentoney, Khalid Azizi, Tobias Jakobi, Jennifer E. Van Eyk, Hugo A. Katus, Christopher C. Glembotski, Shirin Doroudgar Source Type: research