196: Variability in the Pathologic Interpretation of Trans-Bronchial Lung Biopsy after Lung Transplantation. Clinical Implications

Purpose: Heart failure (HF) and the unloading of the myocardium by Left Ventricular Assist Device (LVAD) support have been associated with remodeling of cardiomyocytes and the extracellular matrix (ECM). Integrins (ITG) are membrane spanning proteins connecting the cytoskeleton of cardiomyocytes to the ECM, thereby functioning as mechanotransducers. Given the close connection between the ECM, ITG and cardiomyocytes we investigated changes in ITG expression during HF and LVAD support. Methods and Materials: Frozen left ventricular tissue was obtained during LVAD implantation (pre-LVAD) and at time of heart transplantation (post-LVAD) from 8 patients with dilated cardiomyopathy (DCM) and 8 patients with ischemic heart disease (IHD). Five healthy heart samples served as controls. mRNA-expression of several ITG (Alpha1,3,5,6,7,10,11 and Beta1,3,5,6) was investigated by Q-PCR using a low density array. Immunohistochemistry (IH) and Western blot (WB) analysis were used to localize and quantify protein expression of ITG-A5,-A6,-A7 and -B1. Results: In DCM and IHD combined ITG-A1,-A6,-A10 and -B6 mRNA levels increased during LVAD support (p 0.05). ITG-A7 was significantly elevated pre-LVAD and returned to control levels after LVAD support. In DCM alone ITG-A1,-A6 and -A10 increased significantly during LVAD support (1.1, 1.5 and 2.6 fold respectively, p 0.05) In IHD alone ITG-A6 increased 1.1 fold (p 0.05). IH showed a membraneous staining of ITG-A7 and ITG-B1, whereas ITG-A6 only stained capillaries and ITG-A5 only larger vessels and stroma. The staining pattern preand post-LVAD was not different, but less organized than in control samples. WB showed a low ITG protein level preand post-LVAD compared to controls. Interestingly, Q-PCR and WB showed an increase of ITG-A5 in DCM and a decrease in IHD after LVAD support. Conclusions: The changes in cardiomyocyte make-up and ECM composition during HF are associated with alterations in ITG expression pattern and are altered by ventricular unloading by LVAD, re-inforcing the important role of ITG in mechanotransduction. Supported by the NHF 2004T31