| Abstract | Overproduction of tumor necrosis factor-alpha (TNF-alpha) contributes to cardiac dysfunction associated with systemic or myocardial stress, such as endotoxemia and myocardial ischemia/reperfusion (I/R). Heat shock has been demonstrated to enhance cardiac functional resistance to I/R. However, the protective mechanisms remain unclear. The purpose of this study was to determine: (1) whether cardiac macrophages express heat shock protein 72 (HSP72) after heat shock, (2) whether induced cardiac HSP72 suppresses myocardial TNF-alpha production during I/R, and (3) whether preservation of postischemic myocardial function by heat shock is correlated with attenuated TNF-alpha production during I/R. Rats were subjected to heat shock (42 degrees C for 15 min) and 24 h recovery. Immunoblotting confirmed the expression of cardiac HSP72. Immunofluorescent staining detected HSP72 in cardiac interstitial cells including resident macrophages rather than myocytes. Global I/R caused a significant increase in myocardial TNF-alpha. The increase in myocardial TNF-alpha was blunted by prior heat shock and the reduced myocardial TNF-alpha level was correlated with improved cardiac functional recovery. This study demonstrates for the first time that heat shock induces HSP72 in cardiac resident macrophages and inhibits myocardial TNF-alpha production during I/R. These observations suggest that inhibition of myocardial TNF-alpha production may be a mechanism by which HSP72 protects the heart against postischemic dysfunction. |
| Authors | X Meng, A Banerjee, L Ao, D R Meldrum, B S Cain, B D Shames, A H Harken
(Affiliation: Department of Surgery, University of Colorado Health Sciences Center, Denver 80262, USA.)
|
| Journal | Annals of the New York Academy of Sciences
(Ann N Y Acad Sci)
Vol. 874
Pg. 69-82
(Jun 30 1999)
ISSN: 0077-8923 UNITED STATES |
| PMID | 10415522
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
|
| Chemical References |
- HSP72 Heat-Shock Proteins
- Heat-Shock Proteins
- Tumor Necrosis Factor-alpha
|
| Topics |
- Animals
- HSP72 Heat-Shock Proteins
- Heart
(physiopathology)
- Heat-Shock Proteins
(metabolism, physiology)
- Hot Temperature
- Macrophages
(metabolism)
- Male
- Myocardial Ischemia
(physiopathology)
- Myocardial Reperfusion Injury
(metabolism)
- Myocardium
(metabolism, pathology)
- Rats
- Rats, Sprague-Dawley
- Shock
(metabolism)
- Stress, Physiological
(physiopathology)
- Tumor Necrosis Factor-alpha
(antagonists & inhibitors)
|
