Neutralization of interleukin-1ß in the acute phase of myocardial infarction promotes the progression of left ventricular remodeling
Myung-Woo Hwang, MD, PhDa,
Akira Matsumori, MD, PhD*,a,
Yutaka Furukawa, MD, PhDa,
Koh Ono, MD, PhDa,
Masaharu Okada, MD, PhDa,
Atsushi Iwasaki, MD, PhDa,
Masatake Hara, MD, PhDa,
Tadashi Miyamoto, MD, PhDa,
Masanao Touma, MDa and
Shigetake Sasayama, MD, PhDa
a Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Figure 2 Myocardial infarction (MI) in mice. (A) Evolution of representative serial sections of the hearts. Mice without extensive MI involving all of the free wall and apex of the left ventricular (LV) were excluded from the analysis. Note the remarkable dilation of the LV cavity and hypertrophy of the noninfarcted myocardium. Left ventricular dilation and hypertrophy were observed as early as four weeks after the operation. (B) The transthoracic echocardiography study. Note the marked increase in LV end-diastolic dimension, as compared with that in the sham-operated mice. (C) Collagen staining. Note the scar formation in the infarct-related area and the abundant collagen deposition in the interstitial space 12 weeks after coronary ligation, as compared with that in the sham-operated mice (magnification x200).
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Figure 3 Gene expression levels of interleukin-1ß (IL-1ß) were examined in three mice at each point by real-time quantitative reverse transcription-polymerase chain reaction. A rapid increase in IL-1ß gene expression level, peaking at 6 h, was observed in the infarct-related area, and decreased thereafter. In the noninfarcted area, gene expression levels remained upregulated at 12 weeks after the operation. GADPH = glyceraldehyde-3-phosphate dehydrogenase; h(s) = hour(s); ds = days; w(s) = week(s).
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Figure 4 Effect of anti-interleukin-1 (IL-1) treatment (monoclonal antibody) on the progression of left ventricular (LV) remodeling. Neutralization of IL-1ß in the acute phase of myocardial infarction significantly increased total heart weight and LV end-diastolic dimension (LVEDD). There was no significant difference between the vehicle-treated and control (immunoglobulin G [IgG]-treated) groups (four mice in each). n.s. = not significant.
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Figure 5 Effect of anti-interleukin-1ß (IL-1ß) antibody treatment on infarct healing and pro-collagen gene expression. At three days and one week after the operation, collagen accumulation in the infarct-related myocardium was measured as described in the text. Anti–IL-1ß treatment inhibited collagen accumulation in the infarct-related area, which caused a delay in wound healing. Gene expression of type III pro-collagen was suppressed by anti–IL-1ß treatment by one and three days and one week after the operation. There was no significant difference between the vehicle-treated and control (immunoglobulin G [IgG]-treated) groups (four mice in each). Ab = antibody; Col I and III = collagen type I and III, respectively; GADPH = glyceraldehyde-3-phosphate dehydrogenase; n.s. = not significant.
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p < 0.01; **p < 0.05 vs. sham-operated mice;