| Ventricular myocyte caspases are directly responsible for endotoxin-induced cardiac dysfunction. | |
| | |
MedLine Citation:
|
PMID: 15897345 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: Although most of the deleterious effects of sepsis-induced apoptosis have been attributed to increased lymphocyte cell death, caspase activation may directly alter cell function of different organ systems. We postulated that left ventricular (LV) cardiomyocyte caspase activation is directly involved in sepsis-induced heart contractile dysfunction. METHODS AND RESULTS: LV cardiomyocytes isolated 4 hours after rat treatment with endotoxin injection (10 mg/kg) displayed major reductions in contractile reserve and myofilament response to Ca2+. Concomitantly, endotoxin also induced increases in LV cardiomyocyte caspase-3, -8, and -9-like activities, which were associated with sarcomeric structure destruction and cleavage of components of the cardiac myofilament. Interestingly, zVAD.fmk treatment of septic rat prevented LV cardiomyocyte contractile dysfunction, reductions in myofilament response to calcium, troponin T cleavage, and sarcomere destruction. Serum (10%) of endotoxin-treated rats induced contractile dysfunction, caspase-3-like activity increase, and troponin T cleavage of naive LV cardiomyocytes. The effects of septic serum were prevented in LV cardiomyocytes isolated from zVAD.fmk- or zDEVD.cmk-treated rats or LV cardiomyocytes preincubated with zVAD.fmk or zDEVD.cmk. CONCLUSIONS: The results show an important relationship between endotoxin-induced caspase activation and reduced contractile reserve and sarcomere disarray at the level of single LV cardiomyocytes. |
| | |
Authors:
|
Steve Lancel; Olivier Joulin; Raphael Favory; Jean Francois Goossens; Jérome Kluza; Claude Chopin; Pierre Formstecher; Philippe Marchetti; Remi Neviere |
Related Documents
:
|
6487325 - Micro-analysis for coenzyme q10 in endomyocardial biopsies of cardiac patients and data... 19964085 - Feasibility of regional and global left ventricular shape analysis from real-time 3d ec... 20932465 - Right ventricular dysfunction is a strong predictor of developing atrial fibrillation i... 15725155 - The doppler-derived myocardial performance index is determined by both left ventricular... 8444505 - Effect of ventriculotomy on postinfarction ventricular tachycardia in a canine model. 6487325 - Micro-analysis for coenzyme q10 in endomyocardial biopsies of cardiac patients and data... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-05-16 |
Journal Detail:
|
Title: Circulation Volume: 111 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2005 May |
Date Detail:
|
Created Date: 2005-05-24 Completed Date: 2006-01-12 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
|
Languages: eng Pagination: 2596-604 Citation Subset: AIM; IM |
Affiliation:
|
EA 2689, CHRU, and Université de Lille 2, IFR 114 IMPRT, Lille, France. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Calcium / pharmacology Caspases / metabolism* Endotoxins / adverse effects* Heart Diseases / etiology*, pathology Heart Ventricles / enzymology, pathology* Male Microfilaments / pathology Myocardial Contraction Myocytes, Cardiac / enzymology* Rats Rats, Sprague-Dawley Sarcomeres / pathology Sepsis / complications, pathology, physiopathology* Troponin T / metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Endotoxins; 0/Troponin T; 7440-70-2/Calcium; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Restoration of beta-adrenergic receptor signaling and contractile function in heart failure by disru...
Next Document: Identification and characterization of two genes (MIP-1beta, VE-CADHERIN) implicated in acute reject...