Document Detail


Novel mechanisms for caspase inhibition protecting cardiac function with chronic pressure overload.
MedLine Citation:
PMID:  23277091     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Myocyte apoptosis is considered a major mechanism in the pathogenesis of heart failure. Accordingly, manipulations that inhibit apoptosis are assumed to preserve cardiac function by maintaining myocyte numbers. We tested this assumption by examining the effects of caspase inhibition (CI) on cardiac structure and function in C57BL/6 mouse with pressure overload model induced by transverse aortic constriction (TAC). CI preserved left ventricular (LV) function following TAC compared with the vehicle. TAC increased apoptosis in non-myocytes more than in myocytes and these increases were blunted more in non-myocytes by CI. Total myocyte number, however, did not differ significantly among control and TAC groups and there was no correlation between myocyte number and apoptosis, but there was a strong correlation between myocyte number and an index of myocyte proliferation, Ki67-positive myocytes. Despite comparable pressure gradients, LV hypertrophy was less in the CI group, likely attributable to decreased wall stress. Since changes in myocyte numbers did not account for protection from TAC, several other CI-mediated mechanisms were identified including: (a) lessening of TAC-induced fibrosis, (b) augmentation of isolated myocyte contractility, and (c) increased angiogenesis and Ki67-positive myocytes, which were due almost entirely to the non-myocyte apoptosis, but not myocyte apoptosis, with CI. CI maintained LV function following TAC not by protecting against myocyte loss, but rather by augmenting myocyte contractile function, myocyte proliferation, and angiogenesis resulting in reduced LV wall stress, hypertrophy, and fibrosis.
Authors:
Misun Park; Stephen F Vatner; Lin Yan; Shumin Gao; Seunghun Yoon; Grace Jung Ah Lee; Lai-Hua Xie; Richard N Kitsis; Dorothy E Vatner
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-01
Journal Detail:
Title:  Basic research in cardiology     Volume:  108     ISSN:  1435-1803     ISO Abbreviation:  Basic Res. Cardiol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-01     Completed Date:  2013-08-05     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  0360342     Medline TA:  Basic Res Cardiol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  324     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects
Caspase Inhibitors / pharmacology*
Cell Proliferation / drug effects
Connexin 43 / analysis
Fibrosis
Heart / drug effects*,  physiopathology
Hypertrophy, Left Ventricular / prevention & control*
Ki-67 Antigen / analysis
Male
Mice
Mice, Inbred C57BL
Myocardial Contraction / drug effects
Myocytes, Cardiac / pathology
Neovascularization, Physiologic / drug effects
Ventricular Function, Left / drug effects
Grant Support
ID/Acronym/Agency:
AG27211/AG/NIA NIH HHS; HL033107/HL/NHLBI NIH HHS; HL093481/HL/NHLBI NIH HHS; HL095888/HL/NHLBI NIH HHS; HL106511/HL/NHLBI NIH HHS; HL60665/HL/NHLBI NIH HHS; HL69020/HL/NHLBI NIH HHS; P01 AG027211/AG/NIA NIH HHS; P01 HL069020/HL/NHLBI NIH HHS; R01 HL033107/HL/NHLBI NIH HHS; R01 HL060665/HL/NHLBI NIH HHS; R01 HL093481/HL/NHLBI NIH HHS; R01 HL095888/HL/NHLBI NIH HHS; R01 HL106511/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Caspase Inhibitors; 0/Connexin 43; 0/Ki-67 Antigen; 0/Mki67 protein, mouse
Comments/Corrections

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


Previous Document:  Effects of voluntary wheel running on LPS-induced sickness behavior in aged mice.
Next Document:  Variability in UDP-glucuronosyltransferase genes and morphine metabolism: observations from a cross-...