Evolution of isometric active force (AF, panel A) normalized for cross—sectional area and maximum shortening velocity (V_max, panel B) after salbutamol in control (n = 11), fatty (n = 6) rats and diabetic fatty (n = 4) rats and of AF (panel C) normalized for cross—sectional area and V_max (panel D) during fatigue and early recovery phase of fatigue in control (n = 14), fatty (n = 4) rats and diabetic fatty (n = 7) rats.

<p>Values are expressed as mean percent of baseline ± SD.*: <i>P</i> < 0.05 versus baseline. NS = not significant. The y axis in graphs 2A and 2B does not start at zero. ¹The differences are not significant between groups.</p

General characteristics and main mechanical variables at baseline and after 12h of mechanical ventilation of Zucker control, fatty, and diabetic fatty rats.

<p>General characteristics and main mechanical variables at baseline and after 12h of mechanical ventilation of Zucker control, fatty, and diabetic fatty rats.</p

Isometric active force normalized for cross—sectional area in control (n = 25), fatty (n = 10) rats and diabetic fatty (n = 11) rats, at baseline and after 12 hours of mechanical ventilation.

<p>Values are expressed as mean percent of baseline ± SD.*: <i>P</i> < 0.05 versus baseline.</p

Morphometric study of diaphragm in control (n = 5), fatty (n = 5) and diabetic fatty (n = 5) rats at rest.

<p><b>Panel A: Histological characterization of diaphragm using Oil red O, hematein/eosin (bar = 20 μm) and Myosin Heavy Chain (MyHC) isoforms (bar = 50 μm) stainings. Zoom-in of Oil red O stainings are presented in lower panels. Panel B: fiber type composition (%). Panel C: fiber type area (μm²). Panel D: MyHC2A fiber distribution by cross sectional area. Panel E: MyHC2X fiber distribution by cross sectional area.</b> Values are expressed as mean ± SD or percentages ± SD. *: <i>P</i> < 0.05 versus control; **: <i>P</i> < 0.05 versus diabetic fatty. HE = hematoxylin-eosin coloration.</p

General characteristics of healthy and diabetic treated (<i>atorvastatin</i>, 50 mg. kg^-1.day^-1) and control rats.

<p>General characteristics of healthy and diabetic treated (<i>atorvastatin</i>, 50 mg. kg^-1.day^-1) and control rats.</p

Atorvastatin reduces β-Adrenergic dysfunction in rats with diabetic cardiomyopathy - Fig 3

<p><b>Representative western blot and densitometric data reflecting protein expressions of β1-adrenoceptor (Panel A) and β3-adrenoceptor (Panel B) in left ventricles homogenates of healthy or diabetic rats, treated or not by atorvastatin (50 mg kg-1.day-1) during 15 days.</b> Western blot experiments were normalized using proteins using Ponceau S solution. Data are means ± SD (n = 4 to 9). *: <i>p</i><0.05 versus healthy untreated rats; †: <i>p</i><0.05 diabetic statin versus diabetic untreated rats.</p

Active force (% of baseline value) variation of left ventricle papillary muscle exposed to isoproterenol in diabetic rats pretreated with statin (atorvastatin, 50 mg kg-1 day-1) during 15 days (8 rats per group) with or without L-NAME administration.

<p>Control refers to diabetic rats not receiving statin. AF/s = active force normalized per cross-sectional area during isometric contraction. Data are expressed as mean ± SD. NS: non-significant.</p

Representative Western Blot and densitometric data reflecting protein expressions of multidrug resistance protein 4 (MRP4) in left ventricles homogenates of healthy or diabetic rats, treated or not by atorvastatin (50 mg kg-1.day-1) during 15 days.

<p>Western blot experiments were normalized using GAPDH (37kDa). Data are means ± SD (n = 6). *: <i>p</i><0.05 versus healthy untreated rats; †: <i>p</i><0.05 diabetic statin versus diabetic untreated rats.</p

Effects of atorvastatin on the transcriptome of left ventricles of healthy or diabetic rats.

<p>Panel A-B Heat Map of RNA expression profiles in diabetic versus healthy left ventricles (Panel A) or in statin diabetic versus untreated diabetic left ventricles (Panel B); Color scale indicate relative expression ratio for each gene in diabetic versus healthy left ventricle (Panel A) or in statin versus untreated diabetic left ventricle. Panel C-D Volcano Plot for the modification of genes expression by diabetes in heart ventricle (Panel C) and by atorvastatin in diabetic left ventricle (Panel D). The vertical axis represents the <i>p</i> value (-log¹⁰ <i>p</i> value) and the horizontal axis range the fold change (log² ratio) between diabetic and healthy left ventricles (Panel C) or statin diabetic versus untreated diabetic left ventricles (Panel D) (by t-test). Genes in the area delimited in red have a fold change greater than 1.5 with a <i>p</i> value < 0.05. Genes in the area delimited in green have a fold change greater than -1.5 (ratio <0.67) with a <i>p</i> value < 0.05. Panel E Venn diagram representing the differently expressed genes in diabetic versus healthy left ventricles in blue and in statin diabetic versus untreated diabetic left ventricles in red (<i>p</i><0.05). D is for down-regulation in diabetic versus healthy left ventricles, U for up-regulation. The overlapping part represents the genes modified by diabetes as well as statin, with up- or down-regulation for each comparison.</p