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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 reduced SOD1 expression in myocardium. a Representative Western blots of active SOD1. b Densitometric analysis of Western blot results. Values are shown as mean ± SEM (n = 3 per group); *p < 0.05 vs CTRL, #p < 0.05 vs STZ+ NaBu. NaBu sodium butyrate.
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Fig8: HDAC inhibition reduced SOD1 expression in myocardium. a Representative Western blots of active SOD1. b Densitometric analysis of Western blot results. Values are shown as mean ± SEM (n = 3 per group); *p < 0.05 vs CTRL, #p < 0.05 vs STZ+ NaBu. NaBu sodium butyrate.

Mentions: Superoxide dismutase has been implicated in protective effects against myocardial ischemic injury. The levels of SOD1 in the myocardium were examined. As shown in Fig. 8a, all mice treated with sodium butyrate showed an increase in SOD1 level as compared to mice without sodium butyrate treatment. Densitometric analysis also indicates significant increases in SOD1 1evel following HDAC inhibition (Fig. 8b). In addition, the diabetic myocardium demonstrated an increase in superoxide production, which was suppressed by HDAC inhibition (Additional file 1: Figure S2).Fig. 8


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 reduced SOD1 expression in myocardium. a Representative Western blots of active SOD1. b Densitometric analysis of Western blot results. Values are shown as mean ± SEM (n = 3 per group); *p < 0.05 vs CTRL, #p < 0.05 vs STZ+ NaBu. NaBu sodium butyrate.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig8: HDAC inhibition reduced SOD1 expression in myocardium. a Representative Western blots of active SOD1. b Densitometric analysis of Western blot results. Values are shown as mean ± SEM (n = 3 per group); *p < 0.05 vs CTRL, #p < 0.05 vs STZ+ NaBu. NaBu sodium butyrate.
Mentions: Superoxide dismutase has been implicated in protective effects against myocardial ischemic injury. The levels of SOD1 in the myocardium were examined. As shown in Fig. 8a, all mice treated with sodium butyrate showed an increase in SOD1 level as compared to mice without sodium butyrate treatment. Densitometric analysis also indicates significant increases in SOD1 1evel following HDAC inhibition (Fig. 8b). In addition, the diabetic myocardium demonstrated an increase in superoxide production, which was suppressed by HDAC inhibition (Additional file 1: Figure S2).Fig. 8

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