Clin Res Cardiol 100, Suppl 1, April 2011

P647 - Up-regulation of Runx2 and its downstream gene Opn in mice predisposed to calcification after injury
A.-K. Sowa1, J. Erdmann1, H. Schunkert1, Z. Aherrahrou1
1Medizinische Klinik II, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck;
Introduction: Calcification processes play a determinant role in cardiovascular mortality and morbidity. In this study mice were used as model for Dystrophic Cardiac Calcification (DCC) to explore the mechanisms going on during cardiac calcification processes. DCC shares many features with osteogenesis.
Aim: The aim of this study was to analyze the expression-level of transcription-factors involved in osteogenesis and to identify respective target-genes of these for a better understanding of the initiation and development of cardiac and vascular calcification. Methods: DCC-susceptible C3H/He and DCC-resistant C57BL/6 mice (n=3 in each group and time point) were subjected to freeze-thaw-injury to induce calcification. Early at 24 and 72 hours necrotic and healthy myocardium was separated. Cryo-sections from each tissue were prepared for histological analysis and relative-real-time-PCR was used for mRNA quantification.
Results: Using Calcein-staining, calcification-like deposits appear in resistant and susceptible mice 1 day after injury. Calcification progresses in C3H/He but not in C57BL/6 mice over the next 2 days. Among the tested transcription-factors a 30.3-fold up-regulation of Runx2 was detected in calcified tissue of C3H/He as compared to healthy myocardium. Low expression was found for Sox9, Vdr, Nfkb, Msx1, Smad1, Smad2 and Smad4. Based on this finding we further tested downstream-genes of Runx2. In both strains we found a significant up-regulation of Vdr, Col1a2, MMP8, MMP9, MMP13. Based on the genetic background we saw a differential up-regulation of Opn: 372.55-fold induction in C3H/He compared to 64.44-fold induction in C57BL/6 (p= 0,028).
Conclusion: Infiltrating cells that differentiate into osteoblast-like-cells following injury display high expression of Runx2, which may activate Opn and in turn the MMPs-pathway to cleave collagen (type-I, -II, -III). This study suggests that Opn may play a determinant role in myocardial calcification as a downstream gene of Runx2.
Clin Res Cardiol 100, Suppl 1, April 2011
Zitierung mit Vortrags- oder Posternummer s.o.
DOI 10.1007/s00392-011-1100-y