Dataset related to the article "Ca2+ dysregulation in cardiac stromal cells sustains fibro-adipose remodeling in Arrhythmogenic Cardiomyopathy and can be modulated by flecainide"

<p>This record contains raw data related to the article &quot;Ca2+&nbsp;dysregulation in cardiac stromal cells sustains fibro-adipose remodeling in Arrhythmogenic Cardiomyopathy and can be modulated by flecainide&quot;&nbsp;</p> <p>Abstract</p> <p><strong>Background:&nbsp;</strong>Cardiac mesenchymal stromal cells (C-MSC) were recently shown to differentiate into adipocytes and myofibroblasts to promote the aberrant remodeling of cardiac tissue that characterizes arrhythmogenic cardiomyopathy (ACM). A calcium (Ca²⁺) signaling dysfunction, mainly demonstrated in mouse models, is recognized as a mechanism impacting arrhythmic risk in ACM cardiomyocytes. Whether similar mechanisms influence ACM C-MSC fate is still unknown. Thus, we aim to ascertain whether intracellular Ca²⁺&nbsp;oscillations and the Ca²⁺&nbsp;toolkit are altered in human C-MSC obtained from ACM patients, and to assess their link with C-MSC-specific ACM phenotypes.</p> <p><strong>Methods and results:&nbsp;</strong>ACM C-MSC show enhanced spontaneous Ca²⁺&nbsp;oscillations and concomitant increased Ca²⁺/Calmodulin dependent kinase II (CaMKII) activation compared to control cells. This is manly linked to a constitutive activation of Store-Operated Ca²⁺&nbsp;Entry (SOCE), which leads to enhanced Ca²⁺&nbsp;release from the endoplasmic reticulum through inositol-1,4,5-trisphosphate receptors. By targeting the Ca²⁺&nbsp;handling machinery or CaMKII activity, we demonstrated a causative link between Ca²⁺&nbsp;oscillations and fibro-adipogenic differentiation of ACM C-MSC. Genetic silencing of the desmosomal gene PKP2 mimics the remodelling of the Ca²⁺&nbsp;signalling machinery occurring in ACM C-MSC. The anti-arrhythmic drug flecainide inhibits intracellular Ca²⁺&nbsp;oscillations and fibro-adipogenic differentiation by selectively targeting SOCE.</p> <p><strong>Conclusions:&nbsp;</strong>Altogether, our results extend the knowledge of Ca²⁺&nbsp;dysregulation in ACM to the stromal compartment, as an etiologic mechanism of C-MSC-related ACM phenotypes. A new mode of action of flecainide on a novel mechanistic target is unveiled against the fibro-adipose accumulation in ACM.</p>