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Cardiomyocyte Remodeling in Atrial Fibrillation and Hibernating Myocardium: Shared Pathophysiologic Traits Identify Novel Treatment Strategies?

Weil BR, Ozcan C - Biomed Res Int (2015)

Bottom Line: Development of novel therapies for primary and secondary prevention of AF is critical and requires improved understanding of the cellular and molecular mechanisms underlying the AF disease process.These shared features, which include an array of structural, metabolic, and electrophysiologic changes, appear to represent a conserved adaptive myocyte response to chronic stress that involves dedifferentiation towards a fetal phenotype to promote survival.In this review, we discuss the pathophysiology of AF, summarize studies supporting a common remodeling program in AF and hibernating myocardium, and propose future therapeutic implications of this emerging paradigm.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiovascular Medicine, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY, USA.

ABSTRACT
Atrial fibrillation (AF) is the most common arrhythmia and is associated with a high risk of morbidity and mortality. However, there are limited treatment strategies for prevention of disease onset and progression. Development of novel therapies for primary and secondary prevention of AF is critical and requires improved understanding of the cellular and molecular mechanisms underlying the AF disease process. Translational and clinical studies conducted over the past twenty years have revealed that atrial remodeling in AF shares several important pathophysiologic traits with the remodeling processes exhibited by hibernating myocardium that develop in response to chronic ischemia. These shared features, which include an array of structural, metabolic, and electrophysiologic changes, appear to represent a conserved adaptive myocyte response to chronic stress that involves dedifferentiation towards a fetal phenotype to promote survival. In this review, we discuss the pathophysiology of AF, summarize studies supporting a common remodeling program in AF and hibernating myocardium, and propose future therapeutic implications of this emerging paradigm. Ultimately, better understanding of the molecular mechanisms of atrial myocyte remodeling during the onset of AF and the transition from paroxysmal to persistent stages of the disease may facilitate discovery of new therapeutic targets.

No MeSH data available.


Related in: MedlinePlus

The pathophysiology of atrial fibrillation is complex and includes multiple components. Electrical and structural substrates have a significant role in initiation and progression of atrial fibrillation while closely interacting with several other factors.
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Related In: Results  -  Collection


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fig2: The pathophysiology of atrial fibrillation is complex and includes multiple components. Electrical and structural substrates have a significant role in initiation and progression of atrial fibrillation while closely interacting with several other factors.

Mentions: Despite the magnitude of the disease, the precise molecular mechanisms underlying AF remain incompletely understood. Elucidating disease mechanisms at the basic and clinical level is essential to identify novel targets for prevention and treatment of AF. To date, studies have revealed that the pathophysiology of AF is complex and includes multiple components ranging from vulnerable atrial substrate to electrophysiological triggers (Figure 2) [1]. Electroanatomical remodeling of atrial myocytes is an essential component of AF pathogenesis and exhibits features that are similar to those of another cardiac pathology, hibernating myocardium (HM). HM is characterized by an array of structural, metabolic, and electrophysiologic changes that have been suggested to represent myocyte dedifferentiation and a conserved adaptive response to stress, which may also be apparent in atrial myocytes during AF. The adoption of a phenotype characteristic of HM by atrial myocytes may contribute to the initiation and progression of AF. Thus, further understanding of the common mechanisms underlying AF and HM may facilitate the development of novel targets for disease prevention and treatment.


Cardiomyocyte Remodeling in Atrial Fibrillation and Hibernating Myocardium: Shared Pathophysiologic Traits Identify Novel Treatment Strategies?

Weil BR, Ozcan C - Biomed Res Int (2015)

The pathophysiology of atrial fibrillation is complex and includes multiple components. Electrical and structural substrates have a significant role in initiation and progression of atrial fibrillation while closely interacting with several other factors.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4499626&req=5

fig2: The pathophysiology of atrial fibrillation is complex and includes multiple components. Electrical and structural substrates have a significant role in initiation and progression of atrial fibrillation while closely interacting with several other factors.
Mentions: Despite the magnitude of the disease, the precise molecular mechanisms underlying AF remain incompletely understood. Elucidating disease mechanisms at the basic and clinical level is essential to identify novel targets for prevention and treatment of AF. To date, studies have revealed that the pathophysiology of AF is complex and includes multiple components ranging from vulnerable atrial substrate to electrophysiological triggers (Figure 2) [1]. Electroanatomical remodeling of atrial myocytes is an essential component of AF pathogenesis and exhibits features that are similar to those of another cardiac pathology, hibernating myocardium (HM). HM is characterized by an array of structural, metabolic, and electrophysiologic changes that have been suggested to represent myocyte dedifferentiation and a conserved adaptive response to stress, which may also be apparent in atrial myocytes during AF. The adoption of a phenotype characteristic of HM by atrial myocytes may contribute to the initiation and progression of AF. Thus, further understanding of the common mechanisms underlying AF and HM may facilitate the development of novel targets for disease prevention and treatment.

Bottom Line: Development of novel therapies for primary and secondary prevention of AF is critical and requires improved understanding of the cellular and molecular mechanisms underlying the AF disease process.These shared features, which include an array of structural, metabolic, and electrophysiologic changes, appear to represent a conserved adaptive myocyte response to chronic stress that involves dedifferentiation towards a fetal phenotype to promote survival.In this review, we discuss the pathophysiology of AF, summarize studies supporting a common remodeling program in AF and hibernating myocardium, and propose future therapeutic implications of this emerging paradigm.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiovascular Medicine, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY, USA.

ABSTRACT
Atrial fibrillation (AF) is the most common arrhythmia and is associated with a high risk of morbidity and mortality. However, there are limited treatment strategies for prevention of disease onset and progression. Development of novel therapies for primary and secondary prevention of AF is critical and requires improved understanding of the cellular and molecular mechanisms underlying the AF disease process. Translational and clinical studies conducted over the past twenty years have revealed that atrial remodeling in AF shares several important pathophysiologic traits with the remodeling processes exhibited by hibernating myocardium that develop in response to chronic ischemia. These shared features, which include an array of structural, metabolic, and electrophysiologic changes, appear to represent a conserved adaptive myocyte response to chronic stress that involves dedifferentiation towards a fetal phenotype to promote survival. In this review, we discuss the pathophysiology of AF, summarize studies supporting a common remodeling program in AF and hibernating myocardium, and propose future therapeutic implications of this emerging paradigm. Ultimately, better understanding of the molecular mechanisms of atrial myocyte remodeling during the onset of AF and the transition from paroxysmal to persistent stages of the disease may facilitate discovery of new therapeutic targets.

No MeSH data available.


Related in: MedlinePlus