Document Detail


Tuning flux: autophagy as a target of heart disease therapy.
MedLine Citation:
PMID:  21415729     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE OF REVIEW: Despite maximum medical and mechanical support therapy, heart failure remains a relentlessly progressive disorder with substantial morbidity and mortality. Autophagy, an evolutionarily conserved process of cellular cannibalization, has been implicated in virtually all forms of cardiovascular disease. Indeed, its role is context dependent, antagonizing or promoting disease depending on the circumstance. Here, we review current understanding of the role of autophagy in the pathogenesis of heart failure and explore this pathway as a target of therapeutic intervention.
RECENT FINDINGS: In preclinical models of heart disease, cardiomyocyte autophagic flux is activated; indeed, its role in disease pathogenesis is the subject of intense investigation to define mechanism. Similarly, in failing human heart of a variety of etiologies, cardiomyocyte autophagic activity is upregulated, and therapy, such as with mechanical support systems, elicits declines in autophagy activity. However, when suppression of autophagy is complete, rapid and catastrophic cell death occurs, consistent with a model in which basal autophagic flux is required for proteostasis. Thus, a narrow zone of 'optimal' autophagy seems to exist. The challenge moving forward is to tune the stress-triggered autophagic response within that 'sweet spot' range for therapeutic benefit.
SUMMARY: Whereas we have known for some years of the participation of lysosomal mechanisms in heart disease, it is only recently that upstream mechanisms (autophagy) are being explored. The challenge for the future is to dissect the underlying circuitry and titrate the response into an optimal, proteostasis-promoting range in hopes of mitigating the ever-expanding epidemic of heart failure.
Authors:
Min Xie; Cyndi R Morales; Sergio Lavandero; Joseph A Hill
Related Documents :
21323189 - Bilateral fluorescein angiographic findings in unilateral coats' disease.
15876929 - Use of antibiotics in the prevention and treatment of pertussis.
21403579 - The ocular motor features of adult-onset alexander disease: a case and review of the li...
23707929 - Recovery and survival from aging-associated diseases.
21215469 - The relationship between physical, functional capacity and quality of life (qol) among ...
23408099 - Zoonotic disease risk and the bushmeat trade: assessing awareness among hunters and tra...
16799139 - Interleukin-6 in aging and chronic disease: a magnificent pathway.
20704889 - Can infections prevent or cure allergy and autoimmunity?
21323189 - Bilateral fluorescein angiographic findings in unilateral coats' disease.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current opinion in cardiology     Volume:  26     ISSN:  1531-7080     ISO Abbreviation:  Curr. Opin. Cardiol.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-14     Completed Date:  2011-08-05     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  8608087     Medline TA:  Curr Opin Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  216-22     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Autophagy*
Cardiomegaly
Glycogen Storage Disease Type IIb / physiopathology
Heart Failure / drug therapy*,  etiology
Humans
Myocytes, Cardiac*
Signal Transduction
Grant Support
ID/Acronym/Agency:
HL-075173/HL/NHLBI NIH HHS; HL-080144/HL/NHLBI NIH HHS; HL-090842/HL/NHLBI NIH HHS; P30 HL101254/HL/NHLBI NIH HHS; R01 HL075173/HL/NHLBI NIH HHS; R01 HL080144/HL/NHLBI NIH HHS; R01 HL090842/HL/NHLBI NIH HHS; T32 HL007360/HL/NHLBI NIH HHS; U01 HL100401/HL/NHLBI NIH HHS
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Medical DNA sequencing.
Next Document:  New findings of lysosomal proteolysis in skeletal muscle.