Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Department of Myocardial Pathology, Tomsk, Russia.
Novosibirsk State Medical University, Department of Pathological Physiology and Clinical Pathophysiology, Novosibirsk, Russia.
Int J Cardiol. 2022 Mar 1;350:55-61. doi: 10.1016/j.ijcard.2022.01.013. Epub 2022 Jan 7.
To 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.
A 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.
After 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.
Gene 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.
评估基质金属蛋白酶（MMP）-2 和 9 及其基因多态性（MMP-2(rs243865) 和 MMP-9(rs3918242)）在 24 个月期间无既往心血管疾病（CVD）的女性蒽环类药物诱导性心脏毒性（AIC）病程中的作用。
共纳入 114 例接受阿霉素治疗乳腺癌的 AIC 纽约心脏协会（NYHA）I-III 级患者。
24 个月后，患者乳腺癌缓解，并分为 2 组：AIC 不良病程组（n=54）和无不良病程组（n=60）。与组 2 相比，组 1 患者 MMP-2 血清水平升高 8%（p=0.017），MMP9 升高 18.4%（p<0.001）。组 1 中，MMP-2 水平从 376.8（329.5；426.7）pg/ml 增加至 481.4（389.8；518.7）pg/ml（p<0.001），MMP-9 水平从 23.6（21.4；24.6）pg/ml 增加至 26.0（23.3；27.0）pg/ml（p<0.001）。组 2 中，两组患者 MMP-2 和 MMP-9 水平在 24 个月时均下降。基于 ROC 分析，MMP2≥388.2pg/ml（AUС=0.64；p=0.013）和 MMP-9≥21.25pg/ml（AUС=0.9；p<0.001）水平被确定为 AIHF 不良病程的预测因子。MMP2（rs243865）的 C/C 基因型（OR=4.76；p=0.029）和 MMP-9（rs3918242）的 C/C 基因型（OR=15.2；p<0.0001）与 AIHF 不良病程和 MMP-2 和 MMP-9 水平升高相关。
无既往 CVD 的女性中，MMP-2(rs243865) 和 MMP-9(rs3918242) 基因多态性以及 MMP-2 和 MMP-9 血清水平与 24 个月期间 AIC 的不良病程相关。
