The Downregulation of ADAM17 Exerts Protective Effects against Cardiac Fibrosis by Regulating Endoplasmic Reticulum Stress and Mitophagy

Figure 4

Inhibition of ADAM17 with TMI-005 reduced the degree of post-MI fibrosis and enhanced cardiac function in vivo. C57BL/6 mice were randomly divided into 4 groups, including control, TMI-005, MI, and MI treated with TMI-005. MI groups had left anterior descending ligation for 28 days to induced cardiac fibrosis. (a) Schema of the TMI-005 treatment protocol. (b) ADAM 17 activity in heart tissues was determined by measuring cleavage of the internally quenched fluorogenic substrate MCA-KPLGLDpa-AR-NH2 (). (c, d) In the control and TMI-005 groups, Masson’s trichrome staining and M-mode images were used to assess the collagen deposition and cardiac function. LVESD, LVEDD, LVEF, and LVFS were quantified via echocardiography. (e, f) In the MI and MI treated with TMI-005 groups, Masson’s trichrome staining and M-mode images were used to assess the degree of fibrosis and cardiac function. LVESD, LVEDD, LVEF, and LVFS were quantified via echocardiography. (g) Collagen I and α-SMA expression levels were quantified using western blotting. in each group. Data in (a–g) are expressed as . indicates , and indicates vs. the control or MI groups.

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