keyword

Cardiac myocyte

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https://read.qxmd.com/read/32217149/anti-arrhythmic-properties-of-non-antiarrhythmic-medications
#1
REVIEW
Emmanuel Ato Williams, Vincenzo Russo, Sergio Ceraso, Dhiraj Gupta, Richard Barrett-Jolley
Traditional anti-arrhythmic drugs are classified by the Vaughan-Williams classification scheme based on their mechanisms of action, which includes effects on receptors and/or ion channels. Some known anti-arrhythmic drugs do not perfectly fit into this classification scheme. Other medications/molecules with established non-anti-arrhythmic indications have shown anti-arrhythmic properties worth exploring. In this narrative review, we discuss the molecular mechanisms and evidence base for the anti-arrhythmic properties of traditional non-antiarrhythmic drugs such as inhibitors of the renin angiotensin system (RAS), statins and polyunsaturated fatty acids (PUFAs)...
March 23, 2020: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://read.qxmd.com/read/32212902/a-critical-role-for-estrogen-related-receptor-signaling-in-cardiac-maturation
#2
Tomoya Sakamoto, Timothy R Matsuura, Shibiao Wan, David M Ryba, Junil Kim, Kyoung-Jae Won, Ling Lai, Christopher Petucci, Nataliya Petrenko, Kiran Musunuru, Rick B Vega, Daniel P Kelly
Rationale: The heart undergoes dramatic developmental changes during the prenatal to postnatal transition, including maturation of cardiac myocyte energy metabolic and contractile machinery. Delineation of the mechanisms involved in cardiac postnatal development could provide new insight into the "fetal" shifts that occur in the diseased heart and unveil strategies for driving maturation of stem cell-derived cardiac myocytes. Objective: To delineate transcriptional drivers of cardiac maturation. Methods and Results: We hypothesized that estrogen-related receptors (ERRs) α and γ, known transcriptional regulators of postnatal mitochondrial biogenesis and function, serve a role in the broader cardiac maturation program...
March 26, 2020: Circulation Research
https://read.qxmd.com/read/32210835/diabetes-increases-the-vulnerability-of-the-cardiac-mitochondrial-network-to-criticality
#3
Larissa Vetter, Sonia Cortassa, Brian O'Rourke, Antonis A Armoundas, Djahida Bedja, Johann M E Jende, Martin Bendszus, Nazareno Paolocci, Steven J Sollot, Miguel A Aon, Felix T Kurz
Mitochondrial criticality describes a state in which the mitochondrial cardiac network under intense oxidative stress becomes very sensitive to small perturbations, leading from local to cell-wide depolarization and synchronized oscillations that may escalate to the myocardial syncytium generating arrhythmias. Herein, we describe the occurrence of mitochondrial criticality in the chronic setting of a metabolic disorder, type 1 diabetes (T1DM), using a streptozotocin (STZ)-treated guinea pig (GP) animal model...
2020: Frontiers in Physiology
https://read.qxmd.com/read/32210830/modifications-of-sarcoplasmic-reticulum-function-prevent-progression-of-sarcomere-linked-hypertrophic-cardiomyopathy-despite-a-persistent-increase-in-myofilament-calcium-response
#4
Shamim A K Chowdhury, Chad M Warren, Jillian N Simon, David M Ryba, Ashley Batra, Peter Varga, Evangelia G Kranias, Jil C Tardiff, R John Solaro, Beata M Wolska
Hypertrophic cardiomyopathy (HCM) is a genetic disorder caused by mutations in different genes mainly encoding myofilament proteins and therefore called a "disease of the sarcomere." Despite the discovery of sarcomere protein mutations linked to HCM almost 30 years ago, the cellular mechanisms responsible for the development of this disease are not completely understood and likely vary among different mutations. Moreover, despite many efforts to develop effective treatments for HCM, these have largely been unsuccessful, and more studies are needed to better understand the cellular mechanisms of the disease...
2020: Frontiers in Physiology
https://read.qxmd.com/read/32210653/correlation-of-cardiac-and-liver-iron-level-with-t2-mri-and-vitamin-d3-serum-level-in-patients-with-thalassemia-major
#5
Roya Shaykhbaygloo, Alireza Moradabadi, Hassan Taherahmadi, Mohammad Rafiei, Fariborz Lotfi, Aziz Eghbali
Introduction: Thalassemia is a hypochromic microcytic anemia, which is characterized by congenital disorders. In thalassemia patients, bone diseases are one of the causes of mortality. Our goal was to investigate the association between vitamin D deficiency and increased iron uptake by cardiac myocytes and hepatocytes. Materials and Methods: Forty patients with thalassemia major were studied in Amir Kabir Hospital, Arak, Iran. The information obtained through clinical examination...
2020: Journal of Blood Medicine
https://read.qxmd.com/read/32210298/cyp2j2-modulates-diverse-transcriptional-programs-in-adult-human-cardiomyocytes
#6
Eric A Evangelista, Theresa Aliwarga, Nona Sotoodehnia, Paul N Jensen, Barbara McKnight, Rozenn N Lemaitre, Rheem A Totah, Sina A Gharib
CYP2J2, a member of the Cytochrome P450 family of enzymes, is the most abundant epoxygenase in the heart and has multifunctional properties including bioactivation of arachidonic acid to epoxyeicosatrienoic acids, which, in turn, have been implicated in mediating several cardiovascular conditions. Using a proteomic approach, we found that CYP2J2 expression is lower in cardiac tissue from patients with cardiomyopathy compared to controls. In order to better elucidate the complex role played by CYP2J2 in cardiac cells, we performed targeted silencing of CYP2J2 expression in human adult ventricular cardiomyocytes and interrogated whole genome transcriptional responses...
March 24, 2020: Scientific Reports
https://read.qxmd.com/read/32205183/a-cardiomyocyte-show-of-force-a-fluorescent-alpha-actinin-reporter-line-sheds-light-on-human-cardiomyocyte-contractility-versus-substrate-stiffness
#7
Marcelo C Ribeiro, Rolf H Slaats, Verena Schwach, José M Rivera-Arbelaez, Leon G J Tertoolen, Berend J van Meer, Robert Molenaar, Christine L Mummery, Mireille M A E Claessens, Robert Passier
Cardiovascular disease is often associated with cardiac remodeling, including cardiac fibrosis, which may lead to increased stiffness of the heart wall. This stiffness in turn may cause subsequent failure of cardiac myocytes, however the response of these cells to increased substrate stiffness is largely unknown. To investigate the contractile response of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to increased substrate stiffness, we generated a stable transgenic human pluripotent stem cell line expressing a fusion protein of α-Actinin and fluorescent mRubyII in a previously characterized NKX2...
March 20, 2020: Journal of Molecular and Cellular Cardiology
https://read.qxmd.com/read/32202931/balance-between-rapid-delayed-rectifier-k-current-and-late-na-current-on-ventricular-repolarization-an-effective-antiarrhythmic-target
#8
Bence Hegyi, Ye Chen-Izu, Leighton T Izu, Sridharan Rajamani, Luiz Belardinelli, Donald M Bers, Tamás Bányász
Background - Rapid delayed rectifier K+ current (IKr ) and late Na+ current (INaL ) significantly shape the cardiac action potential (AP). Changes in their magnitudes can cause either long or short QT syndromes (LQT, SQT) associated with malignant ventricular arrhythmias and sudden cardiac death. Methods - Physiological self AP-clamp was used to measure INaL and IKr during the AP in rabbit and porcine ventricular cardiomyocytes in order to test our hypothesis that the balance between IKr and INaL affects repolarization stability in health and disease conditions...
March 23, 2020: Circulation. Arrhythmia and Electrophysiology
https://read.qxmd.com/read/32201924/formalin-pigment-artifact-deposition-in-autopsy-tissue-predisposing-factors-patterns-of-distribution-and-methods-for-removal
#9
Kyriakos Chatzopoulos, Benjamin Van Treeck, Elise Venable, Vishnu Serla, Trenton Wirth, Fazi Amirahmadi, Alissa Peterson, Peter T Lin
Formalin pigment deposition is a known artifact of autopsy histology, often anecdotally associated with decomposition of bodies. However, there is minimal data within the forensic literature demonstrating an association between formalin pigment deposition and length of postmortem interval. Furthermore, there is minimal data concerning other predisposing factors and patterns of distribution of formalin pigment deposition. In this study, we compare the amount and patterns of formalin deposition on histology slides from three categories of death: 1) decomposed bodies, 2) critically ill at time of death, and 3) sudden cardiac death...
March 23, 2020: Forensic Science, Medicine, and Pathology
https://read.qxmd.com/read/32201175/intact-myocardial-preparations-reveal-intrinsic-transmural-heterogeneity-in-cardiac-mechanics
#10
Fotios G Pitoulis, Waseem Hasan, Maria Papadaki, Nicolas G Clavere, Filippo Perbellini, Sian E Harding, Jonathan A Kirk, Samuel Y Boateng, Pieter P de Tombe, Cesare M Terracciano
Determining transmural mechanical properties in the heart provides a foundation to understand physiological and pathophysiological cardiac mechanics. Although work on mechanical characterisation has begun in isolated cells and permeabilised samples, the mechanical profile of living individual cardiac layers has not been examined. Myocardial slices are 300 μm-thin sections of heart tissue with preserved cellular stoichiometry, extracellular matrix, and structural architecture. This allows for cardiac mechanics assays in the context of an intact in vitro organotypic preparation...
March 19, 2020: Journal of Molecular and Cellular Cardiology
https://read.qxmd.com/read/32194354/detection-of-radiation-induced-cardiotoxicity-role-of-echocardiography-and-biomarkers
#11
REVIEW
Radek Pudil
We review the role of echocardiography and biomarkers in detection of radiation-induced cardiac toxicity (RICT). RICT is related to micro- and macrovascular damage which induce inflammation, endothelial dysfunction, accelerated atherosclerosis, myocyte degeneration and fibrosis. The process is cumulative dose to the heart and target volume dependent. Furthermore, the damage of the heart is frequently potentiated by the adjunctive chemotherapy. The clinical manifestations of RICT may acutely develop but most often become clinically apparent several years after irradiation...
May 2020: Reports of Practical Oncology and Radiotherapy
https://read.qxmd.com/read/32193645/four-dimensions-of-the-cardiac-myocyte-epigenome-from-fetal-to-adult-heart
#12
REVIEW
Carolin Rommel, Lutz Hein
PURPOSE OF REVIEW: Development, physiological growth and the response of the heart to injury are accompanied by changes of the transcriptome and epigenome of cardiac myocytes. Recently, cell sorting and next generation sequencing techniques have been applied to determine cardiac myocyte-specific transcriptional and epigenetic mechanisms. This review provides a comprehensive overview of studies analysing the transcriptome and epigenome of cardiac myocytes in mouse and human hearts during development, physiological growth and disease...
March 19, 2020: Current Cardiology Reports
https://read.qxmd.com/read/32190292/mir-140-5p-mediates-bevacizumab-induced-cytotoxicity-to-cardiomyocytes-by-targeting-the-vegfa-14-3-3%C3%AE-signal-pathway
#13
Xuan-Ying Chen, Wei-Lin Huang, Xiao-Ping Peng, Yan-Ni Lv, Jun-He Li, Jian-Ping Xiong
Bevacizumab (BVZ) is the first recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGFA) approved by the FDA for the treatment of different kinds of cancers, especially colorectal cancer. Although the anti-tumor effects have been verified, the side effects of BVZ are also noteworthy, among which, cardiotoxicity may be the most serious side effect of BVZ. However, the exact mechanisms of cardiotoxicity induced by BVZ have been little explored. This study was conducted in vitro in a human cardiac myocyte (HCM) model...
November 1, 2019: Toxicology Research
https://read.qxmd.com/read/32186283/the-effects-of-inhibition-of-microrna-375-in-a-mouse-model-of-doxorubicin-induced-cardiac-toxicity
#14
Hao Zhang, Yikui Tian, Degang Liang, Qiang Fu, Liqun Jia, Dawei Wu, Xinyuan Zhu
BACKGROUND Doxorubicin-induced myocardial toxicity is associated with oxidative stress, cardiomyocyte, apoptosis, and loss of contractile function. Previous studies showed that microRNA-375 (miR-375) expression was increased in mouse models of heart failure and clinically, and that inhibition of miR-375 reduced inflammation and increased survival of cardiomyocytes. This study aimed to investigate the effects and mechanisms of inhibition of miR-375 in a mouse model of doxorubicin-induced cardiac toxicity in vivo and in doxorubicin-treated rat and mouse cardiomyocytes in vitro...
March 18, 2020: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://read.qxmd.com/read/32184125/pdk1-akt-signaling-pathway-regulates-the-expression-and-function-of-cardiac-hyperpolarization-activated-cyclic-nucleotide-modulated-channels
#15
Zhonglin Han, Xiang Wu, Yuan Gao, Xuehua Liu, Jian Bai, Rong Gu, RongFang Lan, Biao Xu, Wei Xu
AIM: The enzyme 3-phosphoinositide-dependent protein kinase-1 (PDK1) is associated with cardiac and pathological remodeling and ion channel function regulation. However, whether it regulates hyperpolarization-activated cyclic nucleotide-modulated channels (HCNs) remains unclear. MAIN METHODS: In the atrial myocytes of heart-specific PDK1 "knockout" mouse model and neonatal mice, protein kinase B (AKT)-related inhibitors or agonists as well as knockdown or overexpression plasmids were used to study the relationship between PDK1 and HCNs...
March 14, 2020: Life Sciences
https://read.qxmd.com/read/32183238/mitochondria-in-the-nuclei-of-rat-myocardial-cells
#16
Chupalav M Eldarov, Irina M Vangely, Valeriya B Vays, Eugene V Sheval, Susanne Holtze, Thomas B Hildebrandt, Natalia G Kolosova, Vasily A Popkov, Egor Y Plotnikov, Dmitry B Zorov, Lora E Bakeeva, Vladimir P Skulachev
Electron microscopic study of cardiomyocytes taken from healthy Wistar and OXYS rats and naked mole rats ( Heterocephalus glaber ) revealed mitochondria in nuclei that lacked part of the nuclear envelope. The direct interaction of mitochondria with nucleoplasm is shown. The statistical analysis of the occurrence of mitochondria in cardiomyocyte nuclei showed that the percentage of nuclei with mitochondria was roughly around 1%, and did not show age and species dependency. Confocal microscopy of normal rat cardiac myocytes revealed a branched mitochondrial network in the vicinity of nuclei with an organization different than that of interfibrillar mitochondria...
March 14, 2020: Cells
https://read.qxmd.com/read/32182359/mechanisms-of-palmitic-acid-conjugated-antisense-oligonucleotide-distribution-in-mice
#17
Alfred E Chappell, Hans J Gaus, Andres Berdeja, Ruchi Gupta, Minji Jo, Thazha P Prakash, Michael Oestergaard, Eric E Swayze, Punit P Seth
Conjugation of antisense oligonucleotide (ASO) with a variety of distinct lipophilic moieties like fatty acids and cholesterol increases ASO accumulation and activity in multiple tissues. While lipid conjugation increases tissue exposure in mice and reduces excretion of ASO in urine, histological review of skeletal and cardiac muscle indicates that the increased tissue accumulation of lipid conjugated ASO is isolated to the interstitium. Administration of palmitic acid-conjugated ASO (Palm-ASO) in mice results in a rapid and substantial accumulation in the interstitium of muscle tissue followed by relatively rapid clearance and only slight increases in intracellular accumulation in myocytes...
March 17, 2020: Nucleic Acids Research
https://read.qxmd.com/read/32178385/stat3-for-cardiac-regenerative-medicine-involvement-in-stem-cell-biology-pathophysiology-and-bioengineering
#18
REVIEW
Shu Nakao, Tasuku Tsukamoto, Tomoe Ueyama, Teruhisa Kawamura
Heart disease is the most common cause of death in developed countries, but the medical treatments for heart failure remain limited. In this context, the development of cardiac regeneration therapy for severe heart failure is important. Owing to their unique characteristics, including multiple differentiation and infinitive self-renewal, pluripotent stem cells can be considered as a novel source for regenerative medicine. Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling plays critical roles in the induction, maintenance, and differentiation of pluripotent stem cells...
March 12, 2020: International Journal of Molecular Sciences
https://read.qxmd.com/read/32173353/saraf-dependent-activation-of-mtorc1-regulates-cardiac-growth
#19
Ayse Sanlialp, Dagmar Schumacher, Leon Kiper, Eshita Varma, Eva Riechert, Thanh Cao Ho, Christoph Hofmann, Vivien Kmietczyk, Frank Zimmermann, Sascha Dlugosz, Angela Wirth, Agnieszka A Gorska, Jana Burghaus, Juan E Camacho Londoño, Hugo A Katus, Shirin Doroudgar, Marc Freichel, Mirko Völkers
Pathological cardiac hypertrophy is an independent risk for heart failure (HF) and sudden death. Deciphering signaling pathways regulating intracellular Ca2+ homeostasis that control adaptive and pathological cardiac growth may enable identification of novel therapeutic targets. The objective of the present study is to determine the role of the store-operated calcium entry-associated regulatory factor (Saraf), encoded by the Tmem66 gene, on cardiac growth control in vitro and in vivo. Saraf is a single-pass membrane protein located at the sarco/endoplasmic reticulum and regulates intracellular calcium homeostasis...
March 12, 2020: Journal of Molecular and Cellular Cardiology
https://read.qxmd.com/read/32172307/clusterin-is-regulated-by-igf1-pi3k-signaling-in-the-heart-implications-for-biomarker-and-drug-target-discovery-and-cardiotoxicity
#20
Sebastian Bass-Stringer, Jenny Y Y Ooi, Julie R McMullen
Open-access gene expression data sets provide a useful resource for identifying novel drug targets and biomarkers. The IGF1-PI3K pathway is a critical mediator of physiological cardiac enlargement/hypertrophy and protection. This study arose after mining a gene microarray data set from a previous study that compared heart tissue from cardiac-specific PI3K transgenic mouse models. The top-ranked candidate identified from the microarray data was clusterin. Clusterin has been proposed as a biomarker for multiple diseases including heart failure, and as a cancer drug target...
March 14, 2020: Archives of Toxicology
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