Mechanisms of cardiac depression caused by lipoteichoic acids from Staphylococcus aureus in isolated rat hearts.

Abstract

BACKGROUND:

Lipoteichoic acid (LTA) represents a major virulence factor in gram-positive sepsis.

METHODS AND RESULTS:

In the present study we perfused isolated rat hearts for 180 minutes with highly purified LTA from Staphylococcus aureus. A progressive decline of left ventricular contractile function paralleled by the expression of myocardial tumor necrosis factor-alpha (TNF-alpha) mRNA and protein as well as the release of TNF-alpha into the perfusate was observed in LTA-perfused hearts. Employment of an anti-TNF-alpha antibody completely prevented the loss in contractile function. When CD14, a prominent pathogen recognition receptor, was blocked by a specific antibody, induction of TNF-alpha mRNA and protein release as well as the associated cardiodepression was diminished in response to LTA. Synthesis of TNF-alpha protein was located to interstitial cells of LTA-challenged hearts as detected by immunohistochemistry. Besides progressive cardiodepression, coronary perfusion pressure (CPP) was moderately increased in LTA-perfused hearts. This was accompanied by the release of thromboxane A2 (TXA2) into the perfusate and the induction of cyclooxygenase (Cox)-2 mRNA and protein in the myocardium. Blocking of TXA2 by the nonspecific Cox inhibitor indomethacin, the thromboxane receptor antagonist daltroban, or the selective Cox-2 inhibitor NS-398 prevented the increase in CPP.

CONCLUSIONS:

LTA causes cardiac depression by activating myocardial TNF-alpha synthesis via CD14 and induces coronary vascular disturbances by activating Cox-2-dependent TXA2 synthesis. These phenomena may contribute to cardiac depression in gram-positive sepsis.

• Authors: Ulrich Grandel, Michael Hopf, Michael Buerke, Katja Hattar, Martina Heep, Ludger Fink, Rainer M Bohle, Siegfried Morath, Thomas Hartung, Soni Pullamsetti, Ralph T Schermuly, Werner Seeger, Friedrich Grimminger, Ulf Sibelius
• Journal: Circulation (Circulation) Vol. 112 Issue 5 Pg. 691-8 (Aug 02 2005) ISSN: 1524-4539 [Electronic] United States
• PMID: 16043646 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipopolysaccharides
• RNA, Messenger
• Teichoic Acids
• Tumor Necrosis Factor-alpha
• lipoteichoic acid

Topics

• Animals
• Disease Models, Animal
• Gene Expression Regulation
• Heart (microbiology)
• Heart Failure (chemically induced, microbiology)
• In Vitro Techniques
• Lipopolysaccharides
• Male
• RNA, Messenger (genetics)
• Rats
• Rats, Wistar
• Staphylococcus aureus (physiology)
• Teichoic Acids
• Tumor Necrosis Factor-alpha (genetics)