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CHANGES IN TYPE IV COLLAGEN AFTER UNLOADING OF THE LEFT VENTRICEL.
Annette H. Bruggink, MSc, Mathijs F.M. van Oosterhout, MD, PhD, Nicolaas de Jonge, MD, PhD, Joyce van Kuik, BSc, Frits H.J. Gmelig-Meyling, PhD and Roel A. de Weger, PhD. Utrecht Netherlands, University Medical Center Utrecht, PO Box 85500 3508 GA, Pathology (H04.312); Utrecht Netherlands, University Medical Center Utrecht, PO Box 85500 3508 GA, Heart Lung Center Utrecht and Utrecht Netherlands, University Medical Center Utrecht, PO Box 85500 3508 GA, Immunology.
Background. Cardiomyocytes are surrounded by a basement membrane which consist of Type IV collagen. The basement membrane links the sarcolema of the individual myocytes to the surrounding extracellular matrix (ECM). Due to unloading of the left ventricle (LV) cardiomyocytes decrease in size and therefore we hypothesize that collagen IV is affected by the reverse remodeling after unloading. Different MMP are able to cleave type IV collagen and will be important in this process.
Methods and Results. LV samples of 26 patients (15 DCM, 11 IHD) were investigated at time of left ventricular assist device (LVAD) implantation (pre-LVAD) at time of heart transplantation (post-LVAD) and of healthy controls (HC). With immunohistochemistry (IHC) we showed that after LVAD support there was a significant decrease in type IV collagen expression. With IHC there was no difference in MMP-1, -8 and -13 expression pre- and post LVAD, however MMP-2 expression was significantly decreased post-LVAD. With Q-PCR, there was no significant difference in MMP-1, -8, and –13 mRNA, in contrast MMP-2 mRNA was significantly increased post-LVAD. Gelatin zymography showed an increase in active MMP-2 after LVAD support, and gelatin in situ zymography (ISZ) a shift of active gelatinase (MMP-2) from the sarcolemma to the ECM was observed after LVAD support. Type IV collagen ISZ showed active MMP in the basement membrane of the cardiomyocyte.
Conclusion: Type IV Collagen is severely affected during reverse remodeling and MMP-2 play an important role in this process.