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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

The time course of measuring the concentration of blood glucose. The peripheral blood concentration was measured on weekly basis. After overnight fasting, blood samples were collected from the tail tip vein on mice. Measurements were performed on control, STZ and STZ+ Sodium butyrate treatment groups, respectively. Mice with blood glucose readings of >250 mg/dl were diagnosed diabetic. Values represent mean ± SEM (n = 5–7 per group); CNTL control; STZ streptozotocin; NaB sodium butyrate.
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Fig1: The time course of measuring the concentration of blood glucose. The peripheral blood concentration was measured on weekly basis. After overnight fasting, blood samples were collected from the tail tip vein on mice. Measurements were performed on control, STZ and STZ+ Sodium butyrate treatment groups, respectively. Mice with blood glucose readings of >250 mg/dl were diagnosed diabetic. Values represent mean ± SEM (n = 5–7 per group); CNTL control; STZ streptozotocin; NaB sodium butyrate.

Mentions: A single injection of STZ (200 mg/kg) was used to induce diabetes in ICR mice. At 1 week after the injection, the fasting blood glucose levels of >450 mg/dl were detected in all mice that received STZ injection. Approximately 20% mice did not survive to sustain the toxicity of STZ by day 14. The surviving mice had blood glucose levels of >450 mg/dl throughout the study period. As shown in Fig. 1, sodium butyrate treatment did not lower the blood glucose level. The two diabetic groups showed no difference in blood glucose level by the end of the study period.Fig. 1


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)

The time course of measuring the concentration of blood glucose. The peripheral blood concentration was measured on weekly basis. After overnight fasting, blood samples were collected from the tail tip vein on mice. Measurements were performed on control, STZ and STZ+ Sodium butyrate treatment groups, respectively. Mice with blood glucose readings of >250 mg/dl were diagnosed diabetic. Values represent mean ± SEM (n = 5–7 per group); CNTL control; STZ streptozotocin; NaB sodium butyrate.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: The time course of measuring the concentration of blood glucose. The peripheral blood concentration was measured on weekly basis. After overnight fasting, blood samples were collected from the tail tip vein on mice. Measurements were performed on control, STZ and STZ+ Sodium butyrate treatment groups, respectively. Mice with blood glucose readings of >250 mg/dl were diagnosed diabetic. Values represent mean ± SEM (n = 5–7 per group); CNTL control; STZ streptozotocin; NaB sodium butyrate.
Mentions: A single injection of STZ (200 mg/kg) was used to induce diabetes in ICR mice. At 1 week after the injection, the fasting blood glucose levels of >450 mg/dl were detected in all mice that received STZ injection. Approximately 20% mice did not survive to sustain the toxicity of STZ by day 14. The surviving mice had blood glucose levels of >450 mg/dl throughout the study period. As shown in Fig. 1, sodium butyrate treatment did not lower the blood glucose level. The two diabetic groups showed no difference in blood glucose level by the end of the study period.Fig. 1

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