Transcriptional regulation of alpha5beta1 integrin, fibronectin, VCAM-1, MCSF-1/c-fms, and MCP-1 in atrioventricular valves after valvular surgery and Staphylococcus aureus bacteremia.
OBJECTIVE
The primary event in the development of infective endocarditis (IE) is bacterial adherence to damaged heart valves. This includes capture, adhesion and internalization of bacteria into host cells.


METHODS
We determined in an experimental rabbit model for IE whether a transient bacteremia caused by Staphylococcus aureus and/or endothelial heart valve lesions induce transcriptional regulation of alpha(5)beta(1) integrin, fibronectin, vascular cell adhesion molecule-1 (VCAM-1), macrophage colony-stimulating factor-1 (MCSF-1), c-fms proto-oncogene (MCSF-1 receptor), and macrophage chemoattractant protein-1 (MCP-1) in mitral and tricuspid valves.


RESULTS
No significant upregulation was found after isolated bacteremia. Six hours after surgical manipulation valvular endothelial lesions led to a distinct modulation in the mRNA expression of proinflammatory cytokines (MCSF-1 and MCP-1), VCAM-1 and alpha(5)beta(1) integrin. The most evident differences between the mitral and tricuspid valves were seen in the significant upregulation of VCAM-1 mRNA on the tricuspid valve in the surgical groups, whereas there was no effect on the mitral valve. MCSF-1 and MCP-1 were dramatically upregulated in both valves after surgery.


CONCLUSIONS
During the host defence mechanisms in the development of IE proinflammatory cytokines, cellular adhesion molecules, and molecules of the fibronectin/integrin axis are activated, showing distinct differences in right- and left-sided heart valves.
Eichinger
Walter Benno
WB
German Heart Center Munich at the Technical University of Munich, Department of Cardiac and Vascular Surgery, Germany.
Grammer
Joachim Burkhard
JB
Zhao
Bo
B
Brückner
Juliane
J
Mendler
Nikolaus
N
Lange
Rüdiger
R
Bauernschmitt
Robert
R
D000818:Animals; D016470:Bacteremia / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D001422:Bacterial Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000235:genetics; D004195:Disease Models, Animal; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006350:Heart Valve Prosthesis; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D008943:Mitral Valve / Q000601:surgery*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013203:Staphylococcal Infections / Q000235:genetics / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000235:genetics; D014158:Transcription, Genetic; D014261:Tricuspid Valve / Q000601:surgery*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D005353:Fibronectins; D016023:Integrins; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D016173:Macrophage Colony-Stimulating Factor