Myocardial remodeling differs between LV and RV myocardium from patients with idiopathic-dilated myocarditis, end-stage heart failure

Abstract

A central event in the development and progression of idiopathic dilated cardiomiopathy (I-DCM) is left ventricular (LV) myocardial remodeling. The aim of the study was to investigate whether extracellular matrix proteins accumulation and matrix metalloproteinases activity differ between RV and LV in I-DCM. Methods: We used explanted hearts from I-DCM patients (n = 4) and hearts from healthy donors (n = 4). Relative LV and RV protein level of MMP-9 and MMP-2 was determined by Western blotting. Zymographic estimation of MMP-9 and MMP-2 activity was assessed. The level of collagene type I was measured with immunoblotting. Quantitative analysis was performed with densitometry. Student’s t test was used to data analysis. Results: both LV myocardial MMP-9 zymographic activity and protein level was increased in I-DCM compared with control (50.53 T 5.3 vs. 21.56 T 3.65, P = 0.0014, and 40.88 T 8.76 vs. 13.8 T 3.5, P = 0.02 respectively), whereas RV myocardial MMP-9 activity was unchanged. MMP-2 myocardial activity in both LV and RV was unchanged in I-DCM compared to control. Amount of collagen type I in LV was significantly higher in I-DCM compared with control (11.79 T 1.4 vs. 6.79 T 0.70, P = 0.009), whereas in RV collagen I level was unchanged. Conclusion: These results demonstrated selective MMP-9 activity upregulation and increased collagen I accumulation in LV myocardium from I-DCM patients. This study demonstrated that extracellular matrix degradation differs between LV and RV myocardium from patients with idiopathic-dilated myocarditis. Our findings suggest that MMP-9 may play an important role in the remodeling in the late stage of heart failure. Further investigations on larger population are needed.