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Effects of pravastatin on progression of glucose intolerance and cardiovascular remodeling in a type II diabetes model

Yang Yu, MD, PhD^*, Koji Ohmori, MD, PhD^*,*, Yan Chen, MD^*, Chubun Sato, PhD, Hideyasu Kiyomoto, MD, PhD^*, Kaori Shinomiya, MD, PhD^*, Hiroto Takeuchi, MD, PhD^*, Katsufumi Mizushige, MD, PhD, FACC^* and Masakazu Kohno, MD, PhD^*

^* Second Department of Internal Medicine
Department of Molecular Biology, Kagawa University School of Medicine, Kagawa, Japan

View larger version (40K): [in a new window]   Figure 1 Comparison of left ventricular inflow velocity patterns at 30 weeks. Early to late diastolic peak velocity ratio was reduced and deceleration of early diastolic inflow was slow in the untreated Otsuka Long-Evans Tokushima Fatty (OLETF) rats (middle). These were normalized in the treated-OLETF rats (right). LETO = Long-Evans Tokushima Otsuka.

View larger version (58K): [in a new window]   Figure 2 A. Representative micrographs of coronary arteries with Azan-Mallory stain at 30 weeks. Arterial wall thickness and perivascular fibrosis were greater in the OLETF rat (middle) than in the LETO rat (left). However, the coronary arterial remodeling was less in the treated-OLETF rat. (right). Scale bar is 50 µm. B. Wall-to-lumen ratio (left) and degree of perivascular fibrosis (right) in LETO, untreated-OLETF, and treated-OLETF rats. Values are expressed as mean ± SD (n = 5 for each group). *p < 0.05 versus LETO rats; p < 0.05 versus untreated-OLETF rats. Abbreviations as in Figure 1.

View larger version (36K): [in a new window]   Figure 3 A. Representative RT-PCR photographs for TGF-ß1, MCP-1, and GAPDH mRNA expression in the left ventricle of age-matched LETO, untreated-OLETF, and treated-OLETF rats at 30 weeks. B. Quantitative comparison of the mRNA expression for TGF-ß1 (left) and MCP-1 (right) in the left ventricle among the groups. Values are the percentage of GAPDH as the control and expressed as mean ± SD (n = 5 for each group). *p < 0.05 versus LETO rats; p < 0.05 versus untreated-OLETF rats. Abbreviations as in Figure 1.

View larger version (81K): [in a new window]   Figure 4 Representative micrographs of immunohistochemistry for transforming growth factor (TGF)-ß1 and monocyte chemoattractant protein (MCP)-1 in the coronary arteries of age-matched LETO (left), untreated-OLETF (middle), and treated-OLETF (right) rats at 30 weeks. Scale bar is 20 µm. Abbreviations as in Figure 1.

View larger version (34K): [in a new window]   Figure 5 A. Representative Western blot photograph for endothelial nitric oxide synthase (eNOS) protein induction in the left ventricle of LETO, untreated-OLETF, and treated-OLETF rats at 30 weeks. B. Quantitative comparison of eNOS protein expression in the left ventricle among the groups. Values are the percentages of the average value of the LETO rats and are expressed as mean ± SD (n = 5 for each group). *p < 0.05 versus LETO rats; p < 0.05 versus untreated-OLETF rats. Abbreviations as in Figure 1.

View larger version (49K): [in a new window]   Figure 6 Representative micrographs of immunohistochemistry for eNOS in the coronary arteries of LETO (left), untreated-OLETF (middle), and treated-OLETF (right) rats at 30 weeks. Scale bar is 20 µm. Abbreviations as in Figures 1 and 5.