Fimasartan for Remodeling after Myocardial Infarction

Figures

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  Figure 1. A schematic diagram of the experimental protocol. echo, echocardiography; Fima, fimasartan; MI, myocardial infarction; PCR, polymerase chain reaction; SD, Sprague–Dawley; PV, pressure–volume; w, week.

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  Figure 2. The anatomy and hemodynamics: (A) The chamber size measurement in M-mode, (B) the chamber size and ejection fraction of the rats during the experiment, and (C) the pressure–volume loops 7 weeks after MI. ■, sham; ▲, MI; ▼, MI + Fima. The MI + Fima group showed a smaller left ventricular volume and larger end-systolic pressure–volume relation (end-systolic pressure–volume relation, red line) compared with the MI-only group. EDPVR, end-diastolic pressure–volume relation; EDP, endo-diastolic pressure; ESPVR, end-systolic pressure–volume relationship; Fima, fimasartan; MI, myocardial infarction; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction. The P-values represent * P < 0.05, ** P < 0.01, and *** P < 0.001. The results are expressed as mean ± SEM (Standard Error Mean).

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  Figure 3. A histologic examination of the explanted hearts: (A) Cardiac hypertrophy was assessed as the heart weight/tibia length ratio. Fimasartan attenuated the induction of cardiac hypertrophy after MI. ■, sham; ▲, MI; ▼, MI + Fima. (B) The hematoxylin and eosin (H&E) and Masson trichrome (MT) staining showed a smaller infarct size and fibrosis in the MI + Fima group. (C) The MI + Fima group (■) had a smaller infarct size than the MI-only group (•). The P-values represent * P < 0.05, and ** P < 0.01. The results are expressed as mean ± SEM.

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  Figure 4. The transcriptional changes in the molecular pathways: (A) The microarray analysis in MI-only and MI + Fima group. In the MI + Fima group, 39 genes were upregulated and 19 genes were downregulated. (B) The clustering analysis showed the upregulation of lipid metabolism and mitochondria membrane ion transporter gene sets in the MI + Fima group. (C) The inflammation and fibrosis inducing genes were downregulated in the MI + Fima group.

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  Figure 5. The change in the cardiomyocyte remodeling and survival signaling with fimasartan: (A) TGF-beta was significantly decreased in the MI + Fima group. (B) The cardiac remodeling regulating molecule ERM and RhoA kinase activity were downregulated in the MI + Fima group. (C) The cell survival regulating molecule -catenin, PTEN, and PDK1 activity were upregulated in the MI + Fima group. The P-values represent * P < 0.05, ** P < 0.01, and *** P < 0.001. The results are expressed as mean ± SEM. ERM, Ezrin, Radoxin and Meosin; PTEN, phosphatase and tensin homologue; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; PDK1, Pyruvate Dehydrogenase Kinase 1.