Local mRNA Expression of Vascular Cell Adhesion Molecule-1 (VCAM-1), Macrophage Colony-Stimulating Factor (MCSF-1), and its Receptor, c-fms, on Rabbit Heart Valves in the Early Phase after Atrioventricular Valve Surgery and Staphylococcus aureus Bacteremia
Übersetzter Titel:
Lokale mRNA Expression von VCAM-1, MCSF-1 und c-fms auf Kaninchen-Herzklappen in der frühen Phase nach AV-Operation und S. aureus Bakteriämie
Objective: To explore the roles of vascular cell adhesion molecule-1 (VCAM-1), macrophage colony-stimulating factor-1 (MCSF-1), and its receptor, c-fms, in the development of bacterial endocardial vegetations and to analyze their effects on valve tissue during bacterial colonization and vegetation growth, we studied their mRNA expression in rabbit heart valves in the early phase after atrioventricular valve surgery and S. aureus bacteremia. Materials and Methods: Seven rabbits received 5*106 colony forming units Staphylococcus aureus i.v.; seven rabbits underwent mitral surgery; seven rabbits underwent tricuspid surgery; seven rabbits underwent both mitral surgery and i.v. S. aureus administration; and seven rabbits underwent both tricuspid surgery and i.v. S. aureus administration. The hearts were explanted 6 hours after the intervention and the valvular tissues were shock frozen in liquid nitrogen. Total RNA was isolated and mRNA abundance determined by semiquantitative duplex RT-PCR using 18S RNA as internal control. Results were compared to the control group consisting of seven untreated rabbits. Results: S.aureus bacteremia alone did not lead to significantly changed mRNA levels of any studied molecules. In the mitral valve, the VCAM-1 expression was not significantly upregulated after mitral surgery and after additional bacteremia, but it was significantly more abundant in the tricuspid valve after tricuspid surgery (p<0.005). Additional S.aureus bacteremia did not result in a further upregulation compared to the isolated tricuspid surgery group (p>0.05). The mRNA expression of MCSF-1 on atrioventricular valves was significantly upregulated after corresponding isolated AV-valve surgery. Moreover, in the mitral valve but not in the tricuspid valve, a significant further increase in MCSF-1 mRNA was observed after additional S.aureus bacteremia (p<0.01 compared to isolated surgery). The mRNA expression of c-fms in atrioventricular valves was significantly downregulated only after corresponding isolated AV-valve surgery (p<0.05). Conclusions: (i) Each heart valve shows a different VCAM-1 response after surgical procedures and S.aureus bacteremia in the early phase. Theremore, considerable interest exists in the role of VCAM-1 in the development of infective endocarditis. (ii) The MCSF-1 mRNA expression level seems to reflect the inflammatory status of the heart valve tissue, i.e. number and differentiation of recruited macrophages. (iii) A necessary negative autocrine feed-back loop may exist between MCSF-1 and c-fms upon traumatic and/or proinflammatory stimuli in heart valves, which leads to downregulation of the receptor in order to elude prolonged stimulation by their own growth factors.
Übersetzte Kurzfassung:
Um die Rolle von VCAM-1, MCSF-1 und c-fms in der Entwicklung von bakteriellen Endocarditis festzustellenen, haben wir deren mRNA-Expression in Kaninchen Herzklappen in der frühen Phase nach AV-Klappen-Operation und S. aureus Bakteriämie via RT-PCR untersucht. Die VCAM-1 Expression war nur wesentlich in der Trikuspidal Klappe nach TK-OP. hochreguliert (p<0.005). Die mRNA-Expression von MCSF-1 in den AV-klappen war deutlich hochreguliert nach der AV-Klappen- OP., Außerdem wurde in der MK aber nicht in der TK ein weiterer Anstieg nach einer zusätzlichen Bakteriämie beobachtet (p<0.01). Die c-fms mRNA Expression in AV-Klappen war nur nach isolierter AV-OP. deutlich Reduziert (p<0.05). Jede Herzklappe zeigt in der frühen Phase nach chirurgischen Eingriffen und S. aureus-Bakteriämie eine unterschiedliche VCAM-1-Antwort. Die Konzentration an MCSF-1 mRNA scheint den entzündlichen Status des Herzklappengewebes. Eine notwendige autokrin-negative Feed-back-Schleife könnte zwischen MCSF-1 und c-fms bestehen.
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