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. 2016 Jun 9;65(10):3111–3128. doi: 10.2337/db15-1563

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© 2016 by the American Diabetes Association.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.

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Injection of Hsp20-enriched exosomes collected from TG cardiomyocytes protects mice against STZ-induced cardiac adverse remodeling. A: DiR-labeled cardiomyocyte-derived exosomes were detectable in mouse cardiomyocytes 1 h after the tail-vein injection in vivo. The right image is magnified from insert square of A. B and C: Exosomal Hsp20 was dose-dependently delivered to the mouse heart after the tail-vein injection. D and E: The time course determination of cardiac Hsp20 levels in TG-Exo–injected mice. F: A scheme of the experimental procedure for the exosome injection in STZ-treated mice. G and H: LVIDd and LVEF% were significantly improved in TG-Exo–injected diabetic mice (n = 5–8). *P < 0.05 vs. buffer/PBS group; #P < 0.05 vs. STZ/PBS group. Full echocardiographic data are listed in Supplementary Table 3. I: Representative TUNEL staining images (red, α-sarcomeric actin for cardiomyocytes; blue, DAPI for nuclear staining; green, apoptotic nuclear; arrows indicate TUNEL-positive nuclei) and quantification results (J) (n = 5 hearts, two sections per heart). *P < 0.05 vs. buffer/PBS group; #P < 0.05 vs. STZ/PBS group. K: Representative merged images of WGA staining (cardiomyocytes, green) and iB4 staining (blood vessels, red). L: The quantified density of myocardial blood microvessels (n = 5 hearts, two sections per heart, detected at low magnification, ×200) (L) and further confirmed by RT-PCR analysis for CD31 expression (n = 5) (M). *P < 0.05 vs. buffer/PBS group; #P < 0.05 vs. STZ/PBS group. D, day; W and wk, week.

Injection of Hsp20-enriched exosomes collected from TG cardiomyocytes protects mice against STZ-induced cardiac adverse remodeling. A: DiR-labeled cardiomyocyte-derived exosomes were detectable in mouse cardiomyocytes 1 h after the tail-vein injection in vivo. The right image is magnified from insert square of A. B and C: Exosomal Hsp20 was dose-dependently delivered to the mouse heart after the tail-vein injection. D and E: The time course determination of cardiac Hsp20 levels in TG-Exo–injected mice. F: A scheme of the experimental procedure for the exosome injection in STZ-treated mice. G and H: LVIDd and LVEF% were significantly improved in TG-Exo–injected diabetic mice (n = 5–8). *P < 0.05 vs. buffer/PBS group; #P < 0.05 vs. STZ/PBS group. Full echocardiographic data are listed in Supplementary Table 3. I: Representative TUNEL staining images (red, α-sarcomeric actin for cardiomyocytes; blue, DAPI for nuclear staining; green, apoptotic nuclear; arrows indicate TUNEL-positive nuclei) and quantification results (J) (n = 5 hearts, two sections per heart). *P < 0.05 vs. buffer/PBS group; #P < 0.05 vs. STZ/PBS group. K: Representative merged images of WGA staining (cardiomyocytes, green) and iB4 staining (blood vessels, red). L: The quantified density of myocardial blood microvessels (n = 5 hearts, two sections per heart, detected at low magnification, ×200) (L) and further confirmed by RT-PCR analysis for CD31 expression (n = 5) (M). *P < 0.05 vs. buffer/PBS group; #P < 0.05 vs. STZ/PBS group. D, day; W and wk, week.