Myh6 promoter-driven Cre recombinase excises floxed DNA fragments in a subset of male germline cells
Myh6-Cre transgenic mouse line was known to express Cre recombinase only in the heart. Nevertheless, during breeding Myh6-Cre to Rosa26fstdTom reporter (tdTom) mouse line, we observed that a significant part of their F2 tdTom/+ offspring had tdTom reporter gene universally activated. Our results show that Myh6-Cre transgenic mice have Cre recombinase activity in a subpopulation of the male germline cells, and that Myh6 gene transcripts are enriched in the interstitial Leydig cells and the undifferentiated spermatogonia stem cells. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - December 28, 2022 Category: Cytology Authors: Caroline Sheldon, Chase W. Kessinger, Yan Sun, Maria I. Kontaridis, Qianyi Ma, Saher Sue Hammoud, Zibei Gao, Hui Zhang, Zhiqiang Lin Source Type: research

The ins and outs of cellular pH during cardiac ischemia
The disease burden associated with cardiovascular disease is largely due to the inability of the heart to block the spread of injury and tissue damage caused by ischemia, which ultimately leads to adverse organ remodelling and heart failure. Current medical interventions have improved outcomes through mechanical reperfusion and drugs that reduce the workload on the damaged heart. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - December 26, 2022 Category: Cytology Authors: Yuanzhao Cao, Nathan J. Palpant Source Type: research

DELE1 is protective for mitochondrial cardiomyopathy
In this study, we report that DELE1 is dispensable for cardiac development and function under baseline conditions. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - December 17, 2022 Category: Cytology Authors: Helen Huynh, Siting Zhu, Sharon Lee, Yutong Bao, Jing Pang, Anh Nguyen, Yusu Gu, Chao Chen, Kunfu Ouyang, Sylvia M. Evans, Xi Fang Source Type: research

CaMKII and reactive oxygen species contribute to early reperfusion arrhythmias, but oxidation of CaMKII δ at methionines 281/282 is not a determining factor
Available evidence suggest that Ca2+/calmodulin-dependent protein kinase type II δ (CaMKIIδ) and reactive oxygen species (ROS) are important in early ischemia-reperfusion arrhythmias (IRA). Since ROS can activate CaMKIIδ by oxidation of two methionines at positions 281/282, oxidized-CaMKIIδ (Ox-CaMKIIδ) has been proposed to be important for IRA. However, direct evidence for this is missing. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - December 14, 2022 Category: Cytology Authors: Marie Haugsten Hansen, Mani Sadredini, Almira Hasic, Mark E. Anderson, Ivar Sjaastad, Mathis Korseberg Stokke Source Type: research

Cardiac injection of USSC boosts remuscularization of the infarcted heart by shaping the T-cell response
Regenerating the injured heart remains one of the most vexing challenges in cardiovascular medicine. Cell therapy has shown potential for treatment of myocardial infarction, but low cell retention so far has limited its success. Here we show that intramyocardial injection of highly apoptosis-resistant unrestricted somatic stem cells (USSC) into infarcted rat hearts resulted in an unprecedented thickening of the left ventricular wall with cTnT+/BrdU+ cardiomyocytes that was paralleled by progressively restored ejection fraction. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - December 6, 2022 Category: Cytology Authors: Zhaoping Ding, Kezhe Tan, Christina Alter, Sebastian Temme, Pascal Bouvain, Christoph Owenier, Sebastian H änsch, Sebastian Wesselborg, Christoph Peter, Stefanie Weidtkamp-Peters, Ulrich Flögel, Jessica Schira-Heinen, Kai Stühler, Julia Hesse, Gesine K Source Type: research

Multi-omics analyses identify molecular signatures with prognostic values in different heart failure aetiologies
Heart failure (HF) is the leading cause of morbidity and mortality worldwide, and there is an urgent need for more global studies and data mining approaches to uncover its underlying mechanisms. Multiple omics techniques provide a more holistic molecular perspective to study pathophysiological events involved in the development of HF. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - December 6, 2022 Category: Cytology Authors: Joseph Pierre Aboumsallem, Canxia Shi, Sanne De Wit, George Markousis-Mavrogenis, Valentina Bracun, Tim R. Eijgenraam, Martijn F. Hoes, Wouter C. Meijers, Elles M. Screever, Marloes E. Schouten, Adriaan A. Voors, Herman H.W. Sillj é, Rudolf A. De Boer Source Type: research

Distinct effects of intracellular vs. extracellular acidic pH on the cardiac metabolome during ischemia and reperfusion
Tissue ischemia results in intracellular pH (pHIN) acidification, and while metabolism is a known driver of acidic pHIN, less is known about how acidic pHIN regulates metabolism. Furthermore, acidic extracellular (pHEX) during early reperfusion confers cardioprotection, but how this impacts metabolism is unclear. Herein we employed LCMS based targeted metabolomics to analyze perfused mouse hearts exposed to: (i) control perfusion, (ii) hypoxia, (iii) ischemia, (iv) enforced acidic pHIN, (v) control reperfusion, and (vi) acidic pHEX (6.8) reperfusion. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - December 5, 2022 Category: Cytology Authors: Alexander S. Milliken, Jessica H. Ciesla, Sergiy M. Nadtochiy, Paul S. Brookes Source Type: research

Adenosine kinase promotes post-infarction cardiac repair by epigenetically maintaining reparative macrophage phenotype
Pro-inflammatory and reparative macrophages are crucial in clearing necrotic myocardium and promoting cardiac repair after myocardial infarction (MI), respectively. Extracellular adenosine has been demonstrated to modulate macrophage polarization through adenosine receptors. However, the role of intracellular adenosine in macrophage polarization has not been explored and adenosine kinase (ADK) is a major enzyme regulating intracellular adenosine levels. Here, we aimed to elucidate the role of ADK in macrophage polarization and its subsequent impact on MI. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - December 3, 2022 Category: Cytology Authors: Min Zhang, Caiping Wang, Rongning Wang, Jiean Xu, Zhefeng Wang, Jianlong Yan, Yongfeng Cai, Liangping Li, Yuqing Huo, Shaohong Dong Source Type: research

dATP elevation induces myocardial metabolic remodeling to support improved cardiac function
Hallmark features of systolic heart failure are reduced contractility and impaired metabolic flexibility of the myocardium. Cardiomyocytes (CMs) with elevated deoxy ATP (dATP) via overexpression of ribonucleotide reductase (RNR) enzyme robustly improve contractility. However, the effect of dATP elevation on cardiac metabolism is unknown. Here, we developed proteolysis-resistant versions of RNR and demonstrate that elevation of dATP/ATP to ~1% in CMs in a transgenic mouse (TgRRB) resulted in robust improvement of cardiac function. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - December 2, 2022 Category: Cytology Authors: Ketaki N. Mhatre, Jason D. Murray, Galina Flint, Timothy S. McMillen, Gerhard Weber, Majid Shakeri, An-Yue Tu, Sonette Steczina, Robert Weiss, David J. Marcinek, Charles E. Murry, Daniel Raftery, Rong Tian, Farid Moussavi-Harami, Michael Regnier Source Type: research

Reactive oxygen species-induced long intergenic noncoding RNA p21 accelerates abdominal aortic aneurysm formation by promoting secretary smooth muscle cell phenotypes
Whether long noncoding RNAs participate in the formation of abdominal aortic aneurysms (AAAs) through the regulation of SMC phenotypic switching is unknown. lincRNA-p21 induced by reactive oxygen species (ROS) is likely functionally associated with SMC phenotypic switching. We thus investigated the role of lincRNA-p21 in SMC phenotypic switching-associated AAA formation and its underlying mechanisms. An analysis of human and mouse abdominal aortic samples revealed that the lincRNA-p21 levels were significantly higher in AAA tissue. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - November 24, 2022 Category: Cytology Authors: Shifei Wang, Junfen Wang, Donghua Cai, Xinzhong Li, Lintao Zhong, Xiang He, Zhongqiu Lin, Yanxian Lai, Hao Zheng, Yilin Zhou, Zhiwen Xiao, Wangjun Liao, Yulin Liao, Jiancheng Xiu, Jianping Bin Source Type: research

Endothelial SIRT6 deficiency promotes arterial thrombosis in mice
Arterial thrombosis may be initiated by endothelial inflammation or denudation, activation of blood-borne elements or the coagulation system. Tissue factor (TF), a central trigger of the coagulation cascade, is regulated by the pro-inflammatory NF- κB-dependent pathways. Sirtuin 6 (SIRT6) is a nuclear member of the sirtuin family of NAD+-dependent deacetylases and is known to inhibit NF-κB signaling. Its constitutive deletion in mice shows early lethality with hypoglycemia and accelerated aging. Of note, the role of SIRT6 in arterial thrombo sis remains unknown. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - November 19, 2022 Category: Cytology Authors: Daniel S. Gaul, Natacha Calatayud, J ürgen Pahla, Nicole R. Bonetti, Yu-Jen Wang, Julien Weber, Samuele Ambrosini, Luca Liberale, Sarah Costantino, Shafeeq A. Mohammed, Simon Kraler, Lambertus J. Van Tits, Lisa Pasterk, Daria Vdovenko, Alexander Akhmedov Source Type: research

Mitochondrial permeability transition pore-dependent necrosis
Mitochondrial permeability transition pore (mPTP)-dependent necrotic cell death is a form of necrotic cell death that is driven by mitochondrial dysfunction by the opening of the mPTP and is triggered by increases in matrix levels of Ca2+ and reactive oxygen species. This form of cell death has been implicated in ischemic injuries of the heart and brain as well as numerous degenerative diseases in the brain and skeletal muscle. This review focuses on the molecular triggers and regulators of mPTP-dependent necrosis in the context of myocardial ischemia reperfusion injury. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - November 18, 2022 Category: Cytology Authors: Dexter J. Robichaux, Mikako Harata, Elizabeth Murphy, Jason Karch Tags: Review article Source Type: research

Intracoronary transplantation of pluripotent stem cell-derived cardiomyocytes: Inefficient procedure for cardiac regeneration
Advances in stem cell biology have facilitated cardiac regeneration, and many animal studies and several initial clinical trials have been conducted using human pluripotent stem cell-derived cardiomyocytes (PSC-CMs). Most preclinical and clinical studies have typically transplanted PSC-CMs via the following two distinct approaches: direct intramyocardial injection or epicardial delivery of engineered heart tissue. Both approaches present common disadvantages, including a mandatory thoracotomy and poor engraftment. (Source: Journal of Molecular and Cellular Cardiology)
Source: Journal of Molecular and Cellular Cardiology - November 17, 2022 Category: Cytology Authors: Hideki Kobayashi, Shugo Tohyama, Hideaki Kanazawa, Hajime Ichimura, Shuji Chino, Yuki Tanaka, Yota Suzuki, Jian Zhao, Naoko Shiba, Shin Kadota, Kazumasa Narita, Takafumi Naito, Tatsuichiro Seto, Koichiro Kuwahara, Yuji Shiba, Keiichi Fukuda Source Type: research

Iron homeostasis in the heart: Molecular mechanisms and pharmacological implications
Iron is necessary for the life of practically all living things, yet it may also harm people toxically. Accordingly, humans and other mammals have evolved an effective and tightly regulatory system to maintain iron homeostasis in healthy tissues, including the heart. Iron deficiency is common in patients with heart failure, and is associated with worse prognosis in this population; while the prevalence of iron overload-related cardiovascular disorders is also increasing. Therefore, enhancing the therapy of patients with cardiovascular disorders requires a thorough understanding of iron homeostasis. (Source: Journal of Mole...
Source: Journal of Molecular and Cellular Cardiology - November 11, 2022 Category: Cytology Authors: Jiawei Zhang, Yijing Song, You Li, Han-Bin Lin, Xuexian Fang Tags: Review article Source Type: research

HuR-dependent expression of Wisp1 is necessary for TGF β-induced cardiac myofibroblast activity
Cardiac fibrosis is regulated by the activation and phenotypic switching of quiescent cardiac fibroblasts to active myofibroblasts, which have extracellular matrix (ECM) remodeling and contractile functions which play a central role in cardiac remodeling in response to injury. Here, we show that expression and activity of the RNA binding protein HuR is increased in cardiac fibroblasts upon transformation to an active myofibroblast. Pharmacological inhibition of HuR significantly blunts the TGF β-dependent increase in ECM remodeling genes, total collagen secretion, in vitro scratch closure, and collagen gel contraction in ...
Source: Journal of Molecular and Cellular Cardiology - November 10, 2022 Category: Cytology Authors: Lisa C. Green, Samuel Slone, Sarah R. Anthony, Adrienne R. Guarnieri, Sharon Parkins, Shannon M. Shearer, Michelle L. Nieman, Sudeshna Roy, Jeffrey Aube, Xiaoqing Wu, Liang Xu, Onur Kanisicak, Michael Tranter Source Type: research