Differences of Matrix Metalloproteinase 2 Expression between Left and Right Ventricles in Response to Nandrolone Decanoate and/or Swimming Training in Mice

Abstract

Background: Matrix metalloproteinase (MMP)-2 plays an important role in the remodeling of left ventricles (LVs) and right ventricles (RVs). We investigated the differences of MMP-2 expression between LV and RV in response to nandrolone decanoate (ND), swimming training (ST), and combined ND and ST (NS) in mice, based on their structural, functional, and biochemical characteristics.

Methods: Totally 28 male C57B1 mice (6 weeks old; 20-23 g) were divided into four groups, including the control (n = 7), ND (n = 6), ST (n = 8), and NS (n = 7) groups. After respective treatments for 8 weeks, echocardiographic examination was used to assess the cardiac structure and function. Van Gieson stain was used to examine the fibrosis of LV and RV in response to different treatments, and Western blotting analysis was performed to explore different MMP-2 expressions between LV and RV in response to ND and/or ST. Analysis of variance was used for comparing the four groups.

Results: At 8 weeks, right ventricular dimension/body weight in the ND group was larger than the other three groups (F = 7.12, P < 0.05) according to the echocardiographic examination. Fibrosis induced by ND administration was increased more in RV (2.59%) than that in LV (2.21%). MMP-2 expression of the ND group in RV was significantly greater than the control and NS groups in RV and the corresponding ND group in LV.

Conclusion: The experimental data support the hypothesis that ND administration induces greater MMP-2 expression increase in RV compared to LV, leading to consequent RV dilation.

Figure 1

Diagrams of mouse echocardiography at the papillary level of short-axis view in four different treatment groups at 8 weeks. RVD in the ND group was larger compared to the other three groups (arrows). (a) Control group; (b) ND group; (c) ST group; (d) NS group. ND: Nandrolone decanoate; ST: Swimming training; NS: Combined nandrolone decanoate and swimming training; RV: Right ventricle; RVD: Right ventricular end-diastolic dimension.

Figure 2

Fibrosis in four different treatment groups of left (a-d) and right ventricles (e-h) of the mice at 8 weeks using Van-Gieson staining. Fibrosis (arrows) in left ventricles of the control (a), ND (b), ST (c), and NS (d) groups; fibrosis (arrows) in right ventricles of the control (e), ND (f), ST (g), and NS (h) groups. ND: Nandrolone decanoate; ST: Swimming training; NS: Combined nandrolone decanoate and swimming training; LV: Left ventricle; RV: Right ventricle.

Figure 3

Relative levels of fibrosis in left and right ventricles in four different treatment groups at 8 weeks. *P < 0.05 compared to the ND group of the left ventricle; ^†P < 0.05 compared to the corresponding control group of the left ventricle; ^‡P < 0.05 compared to the corresponding control group of the right ventricle. ND: Nandrolone decanoate; ST: Swimming training; NS: Combined nandrolone decanoate and swimming training; LV: Left ventricle; RV: Right ventricle.

Figure 4

Different MMP-2 expression in left and right ventricles in four different treatment groups at 8 weeks. *P < 0.05 compared to the corresponding treatment group of left ventricle; ^†P < 0.05 compared to the corresponding control group of left ventricle; ^‡P < 0.05 compared to the corresponding control group of right ventricle. ND: Nandrolone decanoate; ST: Swimming training; NS: Combined nandrolone decanoate and swimming training; LV: Left ventricle; RV: Right ventricle; LV-C: Left ventricle of the control group; RV-C: Right ventricle of the control group; MMP-2: Matrix metalloproteinases-2; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase.