A Transcriptional Switch Governing Fibroblast Plasticity Underlies Reversibility of Chronic Heart Disease

2020 ◽  
Author(s):  
Osvaldo Contreras
1970 ◽  
Vol 12 (3) ◽  
pp. 85-98
Author(s):  
Rasmus Antoft

Chronic illness as biographical occurrence – a study on bypass operated individuals and their biographical work. The primary focus of this article is on bypass operated chronically ill peoples attempt to re-establish their biographical work, their everyday life. The everyday life experiences based on routines and obviousness are subjugated by the chronicle illness influence on the life narrative, its future character and the way in which it affects the shaping of identity, the biographical work. Two different themes are central in individual’s narratives about their everyday life with a chronic heart disease. These themes concern their self-presentation in inter-action with others and their anxiety directed at the future life with the illness, with the anxiety of death. This study shows that every bypass operated and chronically ill participant have experienced difficulties in reshaping their normal biographical work. Their ability to regain social action as part of the biographical work and their shaping of self-identity, has been altered significantly. In various situations this leads to potential stigmatisation, but also to a lack of acceptance in the role-playing of a chronic ill, be that in interaction with strangers or intimate social relations. This causes identity dilemmas, paradoxes in self-presentation and, as a consequence, self-deception in everyday life. The existential problem of anxiety and its subjugating character in the lifeplaning and biographical work is to be explained by the risk of reoccurrence of the heart disease, and by the latency of the possible terminal nature of the disease. The nature of the illness ruptures routines and the predictability of everyday life, thus manifesting itself in key situations of everyday life. In addition to this, the anxiety generates a lack of ability to act actively, that is, the individuals ability actively shape its lifeplaning and its biographical work.


1982 ◽  
Vol 306 (16) ◽  
pp. 954-959 ◽  
Author(s):  
Richard C. Veith ◽  
Murray A. Raskind ◽  
James H. Caldwell ◽  
Robert F. Barnes ◽  
Gail Gumbrecht ◽  
...  

2020 ◽  
Author(s):  
Michael Alexanian ◽  
Pawel F. Przytycki ◽  
Rudi Micheletti ◽  
Arun Padmanabhan ◽  
Lin Ye ◽  
...  

AbstractIn diseased organs, stress-activated signaling cascades alter chromatin, triggering broad shifts in transcription and cell state that exacerbate pathology. Fibroblast activation is a common stress response that worsens lung, liver, kidney and heart disease, yet its mechanistic basis remains poorly understood1,2. Pharmacologic inhibition of the BET family of transcriptional coactivators alleviates cardiac dysfunction and associated fibrosis, providing a tool to mechanistically interrogate maladaptive fibroblast states and modulate their plasticity as a potential therapeutic approach3–8. Here, we leverage dynamic single cell transcriptomic and epigenomic interrogation of heart tissue with and without BET inhibition to reveal a reversible transcriptional switch underlying stress-induced fibroblast activation. Transcriptomes of resident cardiac fibroblasts demonstrated robust and rapid toggling between the quiescent fibroblast and activated myofibroblast state in a manner that directly correlated with BET inhibitor exposure and cardiac function. Correlation of single cell chromatin accessibility with cardiac function revealed a novel set of reversibly accessible DNA elements that correlated with disease severity. Among the most dynamic elements was an enhancer regulating the transcription factor MEOX1, which was specifically expressed in activated myofibroblasts, occupied putative regulatory elements of a broad fibrotic gene program, and was required for TGFβ-induced myofibroblast activation. CRISPR interference of the most dynamic cis-element within the enhancer, marked by nascent transcription, prevented TGFβ-induced activation of Meox1. These findings identify MEOX1 as a central regulator of stress-induced myofibroblast activation associated with cardiac dysfunction. The plasticity and specificity of the BET-dependent regulation of MEOX1 in endogenous tissue fibroblasts provides new trans- and cis- targets for treating fibrotic disease.


1934 ◽  
Vol 10 (1) ◽  
pp. 17-45 ◽  
Author(s):  
David Davis ◽  
A.A. Weinstein ◽  
J.E.F. Riseman ◽  
Herrman L. Blumgart

1997 ◽  
Vol 32 (10) ◽  
pp. 29-35
Author(s):  
E. William Hancock

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