Abstract 1707: Analysis Of Extracellular Matrix Remodeling On Endomyocardial Biopsies From Patients With Inflammatory Cardiomyopathy

Abstract

Introduction: The biopsy based analyse, with histological, immunohistological and molecular biological analysis of myocardial tissues, represents the only possible tool to investigate the basement of inflammatory cardiomyopathy. Since development of this disease assume involvement of extracellular matrix remodelling, the analyze of this process were aimed in this article. Methods and results: Endomyocardial biopsies from patient with inflammatory cardiomyopathy (n=170) were analysed by RT-PCR, Furthermore, histological, immunohistological and biochemical methods (ELISA) were used to estimate the matrix proteins amount in myocardial tissues (n=36). All results were obtained by comparison of patient groups regarding to left ventricular ejection fraction (LVEF), EF>60 versus EF<30. EF<30 group featured significaly increased inflammation cells per surface area: CD3 (p<0.001), CD11a (p<0.02), CD45 (p<0.02), Mac1 (p<0.02) and HLA (p<0.01). The gene expression revealed an increased transcripts number of IL-2 (p<0.01), IL-5 (p<0.01), IL-6 (p<0.02), INF beta (p<0.039), Collagen type I (p<0.001), III (p<0.0014) and IV (p<0.0004) as well Laminin (p<0.001). On the protein level ICTP (p<0.04), MMP9 (p<0.04) and TIMP I (p<0.01) were significaly increased in this group in comparison with EF>60 group. The escalating number of active CD3 cells correlated positively with BNP (ρ=0.624, p<0.0091), adhesion cell number ICAM (ρ=0.682, p<0.01) and VCAM (ρ=0.475, p<0.01) and with uPA (ρ =0.265, p<0.013), as well as with increased quantity of collagen type III per section area (ρ=0.632, p<0.01). The expanded abundance of type I collagen products was clearly dependent of the expression of collagen I gene (ρ=0.575, p<0.002) and uPA (ρ=0.544, p<0.004). Precise correlation between the amount of MMP 9 protein and downward EV values (ρ=− 0.4133, p<0.0073) was also observed in the patient group with EF<30. Conclusion: Myocardial inflammation lead to an imbalance in the MMP/TIMP system with development of myocardial fibrosis with significant correlation to LV-dysfunction. Extracellular matrix remodeling with an imbalance in the MMP/TIMP system plays an important role in the development of left ventricular dysfunction in inflammatory heart disease