In early diabetes, hyperglycemia and the associated metabolic dysregulation promote early changes in the functional properties of cardiomyocytes, progressively leading to the appearance of the diabetic cardiomyopathy phenotype. Recently, the interplay between histone acetyltransferases (HAT) and histone deacetylases (HDAC) has emerged as a crucial factor in the development of cardiac disorders. The present study evaluates whether HDAC inhibition can prevent the development of cardiomyocyte contractile dysfunction induced by a short period of hyperglycemia, with focus on the potential underlying mechanisms. Cell contractility and calcium dynamics were measured in unloaded ventricular myocytes isolated from the heart of control and diabetic rats. Cardiomyocytes were either untreated or exposed to the pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) for 90 min. Then, a fraction of each group of cells was used to evaluate the expression levels of proteins involved in the excitation-contraction coupling, and the cardiomyocyte metabolic activity, ATP content, and reactive oxygen species levels. SAHA treatment was able to counteract the initial functional derangement in cardiomyocytes by reducing cell oxidative damage. These findings suggest that early HDAC inhibition could be a promising adjuvant approach for preventing diabetes-induced cardiomyocyte oxidative damage, which triggers the pro-inflammatory signal cascade, mitochondrial damage, and ventricular dysfunction.
机构:
Southern Med Univ, Dept Urol, Nanfang Hosp, Guangzhou, Guangdong, Peoples R China
Hunan Normal Univ, Dept Emergency, Hunan Prov Peoples Hosp, Affiliated Hosp 1, Changsha, Hunan, Peoples R ChinaSouthern Med Univ, Dept Urol, Nanfang Hosp, Guangzhou, Guangdong, Peoples R China
Shi, Xuan-Yan
Ding, Wei
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Southern Med Univ, Dept Urol, Nanfang Hosp, Guangzhou, Guangdong, Peoples R ChinaSouthern Med Univ, Dept Urol, Nanfang Hosp, Guangzhou, Guangdong, Peoples R China
Ding, Wei
Li, Tie-Qiu
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Hunan Normal Univ, Affiliated Hosp 1, Dept Urol, Hunan Prov Peoples Hosp, Changsha, Hunan, Peoples R ChinaSouthern Med Univ, Dept Urol, Nanfang Hosp, Guangzhou, Guangdong, Peoples R China
Li, Tie-Qiu
Zhang, Yi-Xiong
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Hunan Normal Univ, Dept Emergency, Hunan Prov Peoples Hosp, Affiliated Hosp 1, Changsha, Hunan, Peoples R ChinaSouthern Med Univ, Dept Urol, Nanfang Hosp, Guangzhou, Guangdong, Peoples R China
Zhang, Yi-Xiong
Zhao, Shan-Chao
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Southern Med Univ, Dept Urol, Nanfang Hosp, Guangzhou, Guangdong, Peoples R ChinaSouthern Med Univ, Dept Urol, Nanfang Hosp, Guangzhou, Guangdong, Peoples R China
机构:
Shanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R China
Lab Mol Pathol, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R China
Zhang, Q-L
Wang, L.
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Shanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R China
Lab Mol Pathol, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R China
Wang, L.
Zhang, Y-W
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Shanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R ChinaShanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R China
Zhang, Y-W
Jiang, X-X
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Shanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R China
Lab Mol Pathol, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R China
Jiang, X-X
Yang, F.
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Shanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R China
Lab Mol Pathol, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R China
Yang, F.
Wu, W-L
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Shanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R China
Lab Mol Pathol, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R China
Wu, W-L
Janin, A.
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Lab Mol Pathol, Shanghai, Peoples R China
Univ Paris 07, Hop St Louis, INSERM, Inst Hematol,U728, Paris, FranceShanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R China
Janin, A.
Chen, Z.
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Shanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R China
Lab Mol Pathol, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R China
Chen, Z.
Shen, Z-X
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Shanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R ChinaShanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R China
Shen, Z-X
Chen, S-J
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机构:
Shanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R China
Lab Mol Pathol, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R China
Chen, S-J
Zhao, W-L
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机构:
Shanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R China
Lab Mol Pathol, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Inst Hematol,Shaghai Rui Jin Hosp, Shanghai 200025, Peoples R China