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Histone deacetylase (HDAC) inhibition improves myocardial function and prevents cardiac remodeling in diabetic mice.

Chen Y, Du J, Zhao YT, Zhang L, Lv G, Zhuang S, Qin G, Zhao TC - Cardiovasc Diabetol (2015)

Bottom Line: However, it remains unknown whether HDAC inhibition produces the protective effect in the diabetic heart.Likewise, HDAC inhibition attenuates cardiac hypertrophy, as evidenced by a reduced heart/tibia ratio and areas of cardiomyocytes, which is associated with reduced interstitial fibrosis and decreases in active caspase-3 and apoptotic stainings, but also increased angiogenesis in diabetic myocardium.HDAC inhibition plays a critical role in improving cardiac function and suppressing myocardial remodeling in diabetic heart.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Boston University Medical School, Roger Williams Medical Center, Boston University, 50 Maude Street, Providence, RI, 02908, USA. cyf988@126.com.

ABSTRACT

Background: Recent evidence indicates that inhibition of histone deacetylase (HDAC) protects the heart against myocardial injury and stimulates endogenous angiomyogenesis. However, it remains unknown whether HDAC inhibition produces the protective effect in the diabetic heart. We sought to determine whether HDAC inhibition preserves cardiac performance and suppresses cardiac remodeling in diabetic cardiomyopathy.

Methods: Adult ICR mice received an intraperitoneal injection of either streptozotocin (STZ, 200 mg/kg) to establish the diabetic model or vehicle to serve as control. Once hyperglycemia was confirmed, diabetic mice received sodium butyrate (1%), a specific HDAC inhibitor, in drinking water on a daily basis to inhibit HDAC activity. Mice were randomly divided into following groups, which includes Control, Control + Sodium butyrate (NaBu), STZ and STZ + Sodium butyrate (NaBu), respectively. Myocardial function was serially assessed at 7, 14, 21 weeks following treatments.

Results: Echocardiography demonstrated that cardiac function was depressed in diabetic mice, but HDAC inhibition resulted in a significant functional improvement in STZ-injected mice. Likewise, HDAC inhibition attenuates cardiac hypertrophy, as evidenced by a reduced heart/tibia ratio and areas of cardiomyocytes, which is associated with reduced interstitial fibrosis and decreases in active caspase-3 and apoptotic stainings, but also increased angiogenesis in diabetic myocardium. Notably, glucose transporters (GLUT) 1 and 4 were up-regulated following HDAC inhibition, which was accompanied with increases of GLUT1 acetylation and p38 phosphorylation. Furthermore, myocardial superoxide dismutase, an important antioxidant, was elevated following HDAC inhibition in the diabetic mice.

Conclusion: HDAC inhibition plays a critical role in improving cardiac function and suppressing myocardial remodeling in diabetic heart.

No MeSH data available.


Related in: MedlinePlus

HDAC inhibition promotes angiogenesis in STZ-induced diabetic heart. a, c Representative images of CD31 and α-SMA staining, respectively. b, d quantitative analysis of angiogenetic response. Results were indicated by the number of CD31- or α-SMA-positive cells per mm2. Values are shown as mean ± SEM (n = 3 per group); *p < 0.05 vs CTRL, #p < 0.05 vs STZ+ NaBu; NaBu sodium butyrate. Scale bar 100 µm for CD31, 200 µm for α-SMA.
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Fig9: HDAC inhibition promotes angiogenesis in STZ-induced diabetic heart. a, c Representative images of CD31 and α-SMA staining, respectively. b, d quantitative analysis of angiogenetic response. Results were indicated by the number of CD31- or α-SMA-positive cells per mm2. Values are shown as mean ± SEM (n = 3 per group); *p < 0.05 vs CTRL, #p < 0.05 vs STZ+ NaBu; NaBu sodium butyrate. Scale bar 100 µm for CD31, 200 µm for α-SMA.

Mentions: As shown in Fig. 9a, CD31 positive capillary density was decreased in STZ mice. Administration of sodium butyrate substantially increased the capillary density in myocardium from STZ mice. Furthermore, we examined α-SMA positive microvessels in STZ-induced diabetic mouse hearts. Figure 9c shows α-SMA staining in the heart sections from all treatment groups. There is a significant decrease in α-SMA-positive microvessels in STZ mice as compared to Control group, but HDAC inhibition resulted in a marked increase in microvessels. As shown in Fig. 9b, d, HDAC inhibition increased CD31 and α-SMA positive vessels in the diabetic myocardium.Fig. 9


Histone deacetylase (HDAC) inhibition improves myocardial function and prevents cardiac remodeling in diabetic mice.

Chen Y, Du J, Zhao YT, Zhang L, Lv G, Zhuang S, Qin G, Zhao TC - Cardiovasc Diabetol (2015)

HDAC inhibition promotes angiogenesis in STZ-induced diabetic heart. a, c Representative images of CD31 and α-SMA staining, respectively. b, d quantitative analysis of angiogenetic response. Results were indicated by the number of CD31- or α-SMA-positive cells per mm2. Values are shown as mean ± SEM (n = 3 per group); *p < 0.05 vs CTRL, #p < 0.05 vs STZ+ NaBu; NaBu sodium butyrate. Scale bar 100 µm for CD31, 200 µm for α-SMA.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4527099&req=5

Fig9: HDAC inhibition promotes angiogenesis in STZ-induced diabetic heart. a, c Representative images of CD31 and α-SMA staining, respectively. b, d quantitative analysis of angiogenetic response. Results were indicated by the number of CD31- or α-SMA-positive cells per mm2. Values are shown as mean ± SEM (n = 3 per group); *p < 0.05 vs CTRL, #p < 0.05 vs STZ+ NaBu; NaBu sodium butyrate. Scale bar 100 µm for CD31, 200 µm for α-SMA.
Mentions: As shown in Fig. 9a, CD31 positive capillary density was decreased in STZ mice. Administration of sodium butyrate substantially increased the capillary density in myocardium from STZ mice. Furthermore, we examined α-SMA positive microvessels in STZ-induced diabetic mouse hearts. Figure 9c shows α-SMA staining in the heart sections from all treatment groups. There is a significant decrease in α-SMA-positive microvessels in STZ mice as compared to Control group, but HDAC inhibition resulted in a marked increase in microvessels. As shown in Fig. 9b, d, HDAC inhibition increased CD31 and α-SMA positive vessels in the diabetic myocardium.Fig. 9

Bottom Line: However, it remains unknown whether HDAC inhibition produces the protective effect in the diabetic heart.Likewise, HDAC inhibition attenuates cardiac hypertrophy, as evidenced by a reduced heart/tibia ratio and areas of cardiomyocytes, which is associated with reduced interstitial fibrosis and decreases in active caspase-3 and apoptotic stainings, but also increased angiogenesis in diabetic myocardium.HDAC inhibition plays a critical role in improving cardiac function and suppressing myocardial remodeling in diabetic heart.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Boston University Medical School, Roger Williams Medical Center, Boston University, 50 Maude Street, Providence, RI, 02908, USA. cyf988@126.com.

ABSTRACT

Background: Recent evidence indicates that inhibition of histone deacetylase (HDAC) protects the heart against myocardial injury and stimulates endogenous angiomyogenesis. However, it remains unknown whether HDAC inhibition produces the protective effect in the diabetic heart. We sought to determine whether HDAC inhibition preserves cardiac performance and suppresses cardiac remodeling in diabetic cardiomyopathy.

Methods: Adult ICR mice received an intraperitoneal injection of either streptozotocin (STZ, 200 mg/kg) to establish the diabetic model or vehicle to serve as control. Once hyperglycemia was confirmed, diabetic mice received sodium butyrate (1%), a specific HDAC inhibitor, in drinking water on a daily basis to inhibit HDAC activity. Mice were randomly divided into following groups, which includes Control, Control + Sodium butyrate (NaBu), STZ and STZ + Sodium butyrate (NaBu), respectively. Myocardial function was serially assessed at 7, 14, 21 weeks following treatments.

Results: Echocardiography demonstrated that cardiac function was depressed in diabetic mice, but HDAC inhibition resulted in a significant functional improvement in STZ-injected mice. Likewise, HDAC inhibition attenuates cardiac hypertrophy, as evidenced by a reduced heart/tibia ratio and areas of cardiomyocytes, which is associated with reduced interstitial fibrosis and decreases in active caspase-3 and apoptotic stainings, but also increased angiogenesis in diabetic myocardium. Notably, glucose transporters (GLUT) 1 and 4 were up-regulated following HDAC inhibition, which was accompanied with increases of GLUT1 acetylation and p38 phosphorylation. Furthermore, myocardial superoxide dismutase, an important antioxidant, was elevated following HDAC inhibition in the diabetic mice.

Conclusion: HDAC inhibition plays a critical role in improving cardiac function and suppressing myocardial remodeling in diabetic heart.

No MeSH data available.


Related in: MedlinePlus