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Fibrosis of the left atria during progression of heart failure is associated with increased matrix metalloproteinases in the rat

Christophe Boixel, PhD^*, Vincent Fontaine, PhD^*, Catherine Rücker-Martin, PhD, Paul Milliez, MD, Liliane Louedec, MS^*, Jean-Baptiste Michel, MD, PhD^*, Marie-Paule Jacob, PhD^* and Stéphane N. Hatem, MD, PhD^*,*

^* INSERM Unité 460, Paris, France
Centre d’Exploration Fonctionnelle Intégrée Hôpital Xavier Bichat, Paris, France
CNRS-UMR 8078, Hôpital Marie Lannelongue, 92350 Le Plessis Robinson, France
INSERM Unité 572, Hôpital Lariboisière, Paris, France

View larger version (143K): [in a new window]   Figure 1 Two-dimensional echocardiographic image (parasternal long-axis view) of the heart in sham-operated (A) and infarcted (severe heart failure) (C) rats. M-mode echocardiograms were obtained from the two-dimensional long-axis views, with a cross-section at the level of the aortic valve in sham-operated (B) and infarcted (D) rats. Ao = aorta; LA = left atria; LV = left ventricle.

View larger version (91K): [in a new window]   Figure 2 Masson’s trichrome (A, B) and picrosirius staining (C, D) of atrial sections from control (A, C) and infarcted rats in severe heart failure (B) and mild heart failure (D). Fibrosis is especially visible around myocytes of diseased atria. Sarcomeric alpha-actinin immunostaining of atrial cryosections from control (E) and infarcted (F) rats in severe heart failure (confocal microscopy) showing myolysis of myocytes of diseased atria. Bar = 50 µm (A, B) and 10 µm (C to F).

View larger version (50K): [in a new window]   Figure 3 MMP and TIMP activities in atrial myocardium. (A) Gelatin (MMP-2) and casein (MMP-7) zymogram showing the proteolytic activity in sham-operated (Sh), and infarcted rats in mild (M) or severe (S) heart failure. (B) Western blot of proteins from Sh, M, and S rats probed with anti-MMP-2, anti-MMP-7, and anti-MMP-13 antibodies. Analysis of TIMP-1 and -2 activity by reverse zymography (C) and (D) Western blot performed with anti-TIMP-1, anti-TIMP-2 in Sh, M, and S rats.

View larger version (98K): [in a new window]   Figure 4 Frozen atrial sections stained with anti-alpha-actinin sarcomeric (red), anti-MMP-2 (green) (A, B), and anti-MMP-7 (green) (E, F) from sham (A, C, E) and infarcted (B, D, F) rats in severe heart failure. Arrow in panel F indicates peripheral cell staining. Note that distinct magnifications were used in panel A, B (x20) and C to F (x40); Bar = 20 µm.