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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

Effects of HDAC inhibition on cardiac function in STZ-induced diabetic heart. Echocardiographic measurements of ventricular functional parameters includes: a Ejection fraction; b fractional shortening; c Representative echocardiographic M-mode images. Values are shown as mean ± SEM (n = 5–7 per group); *p < 0.05 vs STZ+ NaBu. NaBu sodium butyrate.
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Fig2: Effects of HDAC inhibition on cardiac function in STZ-induced diabetic heart. Echocardiographic measurements of ventricular functional parameters includes: a Ejection fraction; b fractional shortening; c Representative echocardiographic M-mode images. Values are shown as mean ± SEM (n = 5–7 per group); *p < 0.05 vs STZ+ NaBu. NaBu sodium butyrate.

Mentions: Serial echocardiography was performed immediately before and up to 21 weeks after treatments. As shown in Fig. 2, STZ induced diabetic mice displayed cardiac dysfunction, as indicated by the reduction of both EF and FS as compared to Control group. However, administration of sodium butyrate resulted in improvements in EF and FS as compared with STZ group (Fig. 2a, b). The representative images of M-mode among groups are shown in Fig. 2c. Furthermore, an increase in left ventricular internal dimension (LVID) was observed in STZ-treated group as compared with Control and Control + NaBu groups starting at 7 weeks following STZ injection throughout the 21-week period. LVID;s was significantly reduced in sodium butyrate-treated STZ mice as compared with STZ diabetic mice without treatment (Additional file 1: Table S1). In addition, STZ-induced diabetic mice demonstrated an increase in LVPW, which was also attenuated by treatment of animals with sodium butyrate (Additional file 1: Table S1).Fig. 2


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)

Effects of HDAC inhibition on cardiac function in STZ-induced diabetic heart. Echocardiographic measurements of ventricular functional parameters includes: a Ejection fraction; b fractional shortening; c Representative echocardiographic M-mode images. Values are shown as mean ± SEM (n = 5–7 per group); *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

Fig2: Effects of HDAC inhibition on cardiac function in STZ-induced diabetic heart. Echocardiographic measurements of ventricular functional parameters includes: a Ejection fraction; b fractional shortening; c Representative echocardiographic M-mode images. Values are shown as mean ± SEM (n = 5–7 per group); *p < 0.05 vs STZ+ NaBu. NaBu sodium butyrate.
Mentions: Serial echocardiography was performed immediately before and up to 21 weeks after treatments. As shown in Fig. 2, STZ induced diabetic mice displayed cardiac dysfunction, as indicated by the reduction of both EF and FS as compared to Control group. However, administration of sodium butyrate resulted in improvements in EF and FS as compared with STZ group (Fig. 2a, b). The representative images of M-mode among groups are shown in Fig. 2c. Furthermore, an increase in left ventricular internal dimension (LVID) was observed in STZ-treated group as compared with Control and Control + NaBu groups starting at 7 weeks following STZ injection throughout the 21-week period. LVID;s was significantly reduced in sodium butyrate-treated STZ mice as compared with STZ diabetic mice without treatment (Additional file 1: Table S1). In addition, STZ-induced diabetic mice demonstrated an increase in LVPW, which was also attenuated by treatment of animals with sodium butyrate (Additional file 1: Table S1).Fig. 2

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