scholarly journals Plakophilin-2 truncating variants impair cardiac contractility by disrupting sarcomere stability and organization

2021 ◽  
Vol 7 (42) ◽  
Author(s):  
Kehan Zhang ◽  
Paige E. Cloonan ◽  
Subramanian Sundaram ◽  
Feng Liu ◽  
Shoshana L. Das ◽  
...  
Keyword(s):  
Cardiac Contractility ◽  
Plakophilin 2

scholarly journals Calcium as a Key Player in Arrhythmogenic Cardiomyopathy: Adhesion Disorder or Intracellular Alteration?

2019 ◽  
Vol 20 (16) ◽  
pp. 3986 ◽  
Author(s):  
Francesco Moccia ◽  
Francesco Lodola ◽  
Ilaria Stadiotti ◽  
Chiara Assunta Pilato ◽  
Milena Bellin ◽  
...  
Keyword(s):  
Cardiac Contractility ◽  
Induced Pluripotent Stem Cell ◽  
Arrhythmogenic Cardiomyopathy ◽  
Mechanical Coupling ◽  
Plakophilin 2 ◽  
Genes Encoding ◽  
Life Threatening ◽  
Delayed Afterdepolarizations ◽  
Induced Pluripotent

Arrhythmogenic cardiomyopathy (ACM) is an inherited heart disease characterized by sudden death in young people and featured by fibro-adipose myocardium replacement, malignant arrhythmias, and heart failure. To date, no etiological therapies are available. Mutations in desmosomal genes cause abnormal mechanical coupling, trigger pro-apoptotic signaling pathways, and induce fibro-adipose replacement. Here, we discuss the hypothesis that the ACM causative mechanism involves a defect in the expression and/or activity of the cardiac Ca2+ handling machinery, focusing on the available data supporting this hypothesis. The Ca2+ toolkit is heavily remodeled in cardiomyocytes derived from a mouse model of ACM defective of the desmosomal protein plakophilin-2. Furthermore, ACM-related mutations were found in genes encoding for proteins involved in excitation‒contraction coupling, e.g., type 2 ryanodine receptor and phospholamban. As a consequence, the sarcoplasmic reticulum becomes more eager to release Ca2+, thereby inducing delayed afterdepolarizations and impairing cardiac contractility. These data are supported by preliminary observations from patient induced pluripotent stem-cell-derived cardiomyocytes. Assessing the involvement of Ca2+ signaling in the pathogenesis of ACM could be beneficial in the treatment of this life-threatening disease.

Prolonged Exposure to Microgravity Reduces Cardiac Contractility and Initiates Remodeling in Drosophila

2020 ◽  
Author(s):  
Stanley Mark Walls ◽  
Soda Diop ◽  
Ryan Birse ◽  
Lisa Elmen ◽  
Zhouhui Gan ◽  
...  
Keyword(s):  
Prolonged Exposure ◽  
Cardiac Contractility

scholarly journals Loss of plakophilin 2 disrupts heart development in zebrafish

2012 ◽  
Vol 56 (9) ◽  
pp. 711-718 ◽  
Author(s):  
Miriam A. Moriarty ◽  
Rebecca Ryan ◽  
Pierce Lalor ◽  
Peter Dockery ◽  
Lucy Byrnes ◽  
...  
Keyword(s):  
Heart Development ◽  
Plakophilin 2

Cardioprotective and Vasoprotective Effects of Corticotropin-Releasing Hormone and Urocortins: Receptors and Signaling

2021 ◽  
pp. 107424842098530
Author(s):  
Sergey V. Popov ◽  
Ekaterina S. Prokudina ◽  
Alexander V. Mukhomedzyanov ◽  
Natalia V. Naryzhnaya ◽  
Huijie Ma ◽  
...  
Keyword(s):  
Mitochondrial Permeability Transition ◽  
Vascular Endothelial Cells ◽  
Isolated Heart ◽  
Cardiac Contractility ◽  
Permeability Transition Pore ◽  
Chronic Administration ◽  
Permeability Transition ◽  
Janus Kinase ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone

Despite the recent progress in research and therapy, cardiovascular diseases are still the most common cause of death worldwide, thus new approaches are still needed. The aim of this review is to highlight the cardioprotective potential of urocortins and corticotropin-releasing hormone (CRH) and their signaling. It has been documented that urocortins and CRH reduce ischemic and reperfusion (I/R) injury, prevent reperfusion ventricular tachycardia and fibrillation, and improve cardiac contractility during reperfusion. Urocortin-induced increase in cardiac tolerance to I/R depends mainly on the activation of corticotropin-releasing hormone receptor-2 (CRHR2) and its downstream pathways including tyrosine kinase Src, protein kinase A and C (PKA, PKCε) and extracellular signal-regulated kinase (ERK1/2). It was discussed the possibility of the involvement of interleukin-6, Janus kinase-2 and signal transducer and activator of transcription 3 (STAT3) and microRNAs in the cardioprotective effect of urocortins. Additionally, phospholipase-A2 inhibition, mitochondrial permeability transition pore (MPT-pore) blockade and suppression of apoptosis are involved in urocortin-elicited cardioprotection. Chronic administration of urocortin-2 prevents the development of postinfarction cardiac remodeling. Urocortin possesses vasoprotective and vasodilator effect; the former is mediated by PKC activation and prevents an impairment of endothelium-dependent coronary vasodilation after I/R in the isolated heart, while the latter includes both cAMP and cGMP signaling and its downstream targets. As CRHR2 is expressed by both cardiomyocytes and vascular endothelial cells. Urocortins mediate both endothelium-dependent and -independent relaxation of coronary arteries.

scholarly journals Device interaction between Cardiac‐Contractility‐Modulation (CCM) und subcutaneus Defibrillator (S‐ICD)

2021 ◽  
Author(s):  
Luca Trolese ◽  
Thomas Faber ◽  
Alexander Gressler ◽  
Johannes Steinfurt ◽  
Judith Stuplich ◽  
...  
Keyword(s):  
Cardiac Contractility ◽  
Cardiac Contractility Modulation ◽  
Device Interaction
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