Changes in the Cardiac GHSR1a-Ghrelin System Correlate With Myocardial Dysfunction in Diabetic Cardiomyopathy in Mice

Figures

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  Figure 1.. Changes in levels of myocardial GHSR1a in STZ-induced diabetes in cohort 1. (A) Western blot analysis of GHSR1a in control and STZ-treated mice with cardiac troponin as control. (B) Quantification of Western blot analysis, where data are represented as densitometric ratios of GHSR1a to cardiac troponin. Data are expressed as mean ± standard error of the mean (SEM) (n = 6). *P < 0.05.

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  Figure 2.. Cardiac fibrosis in (A) control and (B) STZ-treated mice from cohort 1. Representative images where blue is increased collagen deposition and red is healthy cardiac tissue.

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  Figure 3.. Fluorescence microscopy analysis of GHSR1a, ghrelin, BNP, and SERCA2a in control and STZ-treated mice. Representative fluorescent images in cohort 2 of (A to D) control and (E to H) STZ-treated mice for GHSR1a, ghrelin, BNP, and SERCA2a. (I) Images were quantified as described in Materials and Methods. There were significant differences between control and STZ-treated mice in levels of GHSR1a and SERCA2a. Data are expressed as mean ± SEM based on independent t tests with significance set at P < 0.05. **P < 0.01.

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  Figure 4.. Correlation of GHSR, ghrelin, and BNP fluorescence intensities with glucose tolerance. Linear regression of ghrelin (green), GHSR1a (red), BNP (blue), and SERCA2a (gray) between the AUC and the raw integrated density. Each dot represents an individual animal, including both the control and the STZ-treated mice. There were significant negative correlations with glucose tolerance and GHSR1a (P = 0.0097, r2 = 0.6632) and SERCA2a (P = 0.0117, r2 = 0.6508) but not with ghrelin (P = 0.0921, r2 = 0.4672) or BNP (P = 0.8324, r2 = 0.2548).

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  Figure 5.. Correlational analyses of GHSR, ghrelin, BNP, and SERCA2a fluorescence intensities. Each point represents an individual mouse from either the control or STZ-treated group in cohort 2. There were significant interactions between (A) ghrelin and GHSR1a, (C) SERCA2a and GHSR1a, and (D) ghrelin and SERCA2a, but there was no significant correlation between (B) BNP and GHSR1a.

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  Figure 6.. Cardiac fibrosis in (A) control and (B) STZ-treated mice from cohort 2. Representative images where blue is increased collagen deposition and red is healthy cardiac tissue.