Document Detail


Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure.
MedLine Citation:
PMID:  15932947     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In this study, we tested whether the human heart possesses a cardiac stem cell (CSC) pool that promotes regeneration after infarction. For this purpose, CSC growth and senescence were measured in 20 hearts with acute infarcts, 20 hearts with end-stage postinfarction cardiomyopathy, and 12 control hearts. CSC number increased markedly in acute and, to a lesser extent, in chronic infarcts. CSC growth correlated with the increase in telomerase-competent dividing CSCs from 1.5% in controls to 28% in acute infarcts and 14% in chronic infarcts. The CSC mitotic index increased 29-fold in acute and 14-fold in chronic infarcts. CSCs committed to the myocyte, smooth muscle, and endothelial cell lineages increased approximately 85-fold in acute infarcts and approximately 25-fold in chronic infarcts. However, p16(INK4a)-p53-positive senescent CSCs also increased and were 10%, 18%, and 40% in controls, acute infarcts, and chronic infarcts, respectively. Old CSCs had short telomeres and apoptosis involved 0.3%, 3.8%, and 9.6% of CSCs in controls, acute infarcts, and chronic infarcts, respectively. These variables reduced the number of functionally competent CSCs from approximately 26,000/cm3 of viable myocardium in acute to approximately 7,000/cm3 in chronic infarcts, respectively. In seven acute infarcts, foci of spontaneous myocardial regeneration that did not involve cell fusion were identified. In conclusion, the human heart possesses a CSC compartment, and CSC activation occurs in response to ischemic injury. The loss of functionally competent CSCs in chronic ischemic cardiomyopathy may underlie the progressive functional deterioration and the onset of terminal failure.
Authors:
Konrad Urbanek; Daniele Torella; Farooq Sheikh; Antonella De Angelis; Daria Nurzynska; Furio Silvestri; C Alberto Beltrami; Rossana Bussani; Antonio P Beltrami; Federico Quaini; Roberto Bolli; Annarosa Leri; Jan Kajstura; Piero Anversa
Related Documents :
9753797 - Canine and feline caval syndrome.
2920577 - Patient and family participation in the management of respiratory failure in duchenne's...
8814477 - Surfactant replacement therapy in acute respiratory distress syndrome from viral pneumo...
8203607 - Control of oxidative metabolism in volume-overloaded rat hearts: effects of different l...
9809937 - Association of chronotropic incompetence with echocardiographic ischemia and prognosis.
15088107 - Glutathione s-transferase gene polymorphism as a susceptibility factor in smoking-relat...
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.     Date:  2005-06-02
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  102     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-06-15     Completed Date:  2005-08-16     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8692-7     Citation Subset:  IM    
Affiliation:
Cardiovascular Research Institute, Department of Medicine, New York Medical College, Valhalla, NY 10595, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Apoptosis / physiology
Blotting, Western
Cell Differentiation / physiology
Cyclin-Dependent Kinase Inhibitor p16 / metabolism
DNA-Binding Proteins
Heart / physiology*
Humans
In Situ Hybridization, Fluorescence
Mitosis / physiology
Multipotent Stem Cells / cytology*,  physiology
Myocardial Infarction / physiopathology*
Myocardium / cytology*
Regeneration / physiology*
Telomerase / metabolism
Telomere / physiology
Grant Support
ID/Acronym/Agency:
AG023071/AG/NIA NIH HHS; AG15756/AG/NIA NIH HHS; AG17042/AG/NIA NIH HHS; HL075480/HL/NHLBI NIH HHS; HL081737/HL/NHLBI NIH HHS; HL38132/HL/NHLBI NIH HHS; HL55757/HL/NHLBI NIH HHS; HL65573/HL/NHLBI NIH HHS; HL65577/HL/NHLBI NIH HHS; HL66923/HL/NHLBI NIH HHS; HL68088/HL/NHLBI NIH HHS; HL70897/HL/NHLBI NIH HHS; HL76794/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cyclin-Dependent Kinase Inhibitor p16; 0/DNA-Binding Proteins; EC 2.7.7.49/Telomerase
Comments/Corrections

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


Previous Document:  A heterodimer-selective agonist shows in vivo relevance of G protein-coupled receptor dimers.
Next Document:  Neuroglobin, nitric oxide, and oxygen: functional pathways and conformational changes.