Extracellular matrix remodeling in anthracycline-induced cardiotoxicity: What place on the pedestal?

Abstract

ObjectiveTo evaluate the role of matrix metalloproteinases (MMP)-2 and 9 and the gene polymorphisms of MMP-2 (rs243865) and MMP-9 (rs3918242) in the course of anthracycline-induced cardiotoxicity (AIC) in women without previous cardiovascular diseases (CVD) during 24-months. MethodsA total of 114 women (47.0 [44.0; 52.0] years old) with AIC of NYHA class I-III who received doxorubicin for breast cancer were enrolled. ResultsAfter 24 months patients had breast cancer remission and were divided into 2 groups: group 1 comprised women with adverse course of AIC (n = 54), group 2 comprised those without it (n = 60). Serum levels of MMP-2 were higher by 8% (p = 0.017) MMP9 by 18.4% (p < 0.001) in group 1 than in group 2. In group 1 the levels of MMP-2 increased (p < 0.001) from 376.8 (329.5; 426.7) to 481.4 (389.8; 518.7) pg/mL, and MMP-9 increased (p < 0.001) from 23.6 (21.4; 24.6) to 26.0 (23.3; 27.0) pg/mL at 24 months. In group 2 the both MMP-2 and MMP-9 level decreased at 24 months. Based on ROC-analysis, the levels of MMP2 ≥ 388.2 pg/mL (AUС = 0.64; р = 0.013) and MMP-9 ≥ 21.25 pg/mL (AUС = 0.9; р < 0.001) were identified as predictors for adverse course of AIHF. The presence of C/C genotype of MMP2 (OR = 4.76; p = 0.029) and C/C genotype of MMP-9 (OR = 15.2; p < 0.0001) were related with adverse course of AIHF and higher levels of MMP-2 and MMP-9. ConclusionGene polymorphisms of MMP-2 (rs243865) and MMP-9 (rs3918242) and serum levels of MMP-2 and MMP-9 levels in women without previous CVD were associated with adverse course of AIC during 24 months.