Valvular chondromodulin-1 expression is downregulated in a rabbit model of infective endocarditis.
OBJECTIVE
Tissue neovascularization is a major event in the development and dissemination of inflammatory diseases, such as infective endocarditis (IE). Although the molecular triggers which allow vascular ingrowth in the aforementioned avascular regions are not well understood, they may represent potential prophylactic or therapeutic targets. Thus, an investigation was conducted to determine whether the expression of chondromodulin-1 (Chm-1), an anti-angiogenic protein, is dysregulated in mitral valves in a rabbit model of IE, and whether Chm-1 transcripts are differentially expressed in various heart tissues.


METHODS
Five groups of animals (seven per group) were studied: group I was untreated controls; group II received (intravenously) 6x10(6) colony-forming units of Staphylococcus aureus; group III underwent mitral valve surgery; and groups IV and V underwent surgery and received S. aureus (as per group II), with tissues sampled at 6 and 12 h after surgery, respectively). Mitral valve surgery was performed by sewing a Dacron patch onto the valve, thereby creating a lesion and causing valve insufficiency. Explanted hearts were dissected and Chm-1 expression was determined using both conventional and real-time RT-PCR.


RESULTS
Chm-1 transcripts were found in all cardiac regions, with strong expression in the heart valves, aorta, and pulmonary artery, and lowest expression in the ventricles. Both RT-PCR methods led to similar results; however, the down-regulation of Chm-1 expression in groups III, IV and V compared to controls was more pronounced in the real-time RT-PCR experiments (89 +/- 28% versus 40 +/- 28%; 63 +/- 22% versus 29 +/- 19%; and 51 +/- 11% versus 13 +/- 7.4%; Chm-1/GAPDH ratio levels relative to the control group in conventional versus real-time RT-PCRs in groups III, IV and V, respectively). Only the decrease in group V was significantly different from group I with both methods (p < 0.05 and p = 0.001). Bacteremia alone resulted only in minor changes compared to controls.


CONCLUSIONS
It is concluded that valvular Chm-1 expression is down-regulated in the early phase of IE, which is likely to promote leaflet vascularization and progression of the disease.
Grammer
Joachim B
JB
German Heart Center Munich, Department of Cardiac and Vascular Surgery, Clinic at the Technical University of Munich, Munich, Germany. joachim.grammer@gmx.net
Eichinger
Walter B
WB
Bleiziffer
Sabine
S
Benz
Matthias R
MR
Lange
Rüdiger
R
Bauernschmitt
Robert
R
D000818:Animals; D001011:Aorta / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D004697:Endocarditis, Bacterial / Q000503:physiopathology*; D005260:Female; D020869:Gene Expression Profiling; D006351:Heart Valves / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008943:Mitral Valve / Q000503:physiopathology*; D011651:Pulmonary Artery / Q000378:metabolism; D011817:Rabbits
D008565:Membrane Proteins