Metallothionein Suppresses Angiotensin II–Induced Nicotinamide Adenine Dinucleotide Phosphate Oxidase Activation, Nitrosative Stress, Apoptosis, and Pathological Remodeling in the Diabetic Heart

Zhou, Guihua; Li, Xiaokun; Hein, David W.; Xiang, Xilin; Marshall, James P.; Prabhu, Sumanth D.; Cai, Lu

doi:10.1016/j.jacc.2008.05.019

Cited by 111 publications

(114 citation statements)

References 32 publications

(70 reference statements)

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“…2, 35 Induction of diabetes was associated with 2.9-fold and 1.5-fold increase in angiotensinogen and AT1R mRNA expression in wild-type mice (both P<0.01, Figures 1G,H). AT1R mRNA level was significantly higher in CRP/Con than in Wt/Con (P<0.05).…”

Section: Cardiac Inflammation Ras and Bnpmentioning

confidence: 88%

“…32-34 Diabetic cardiomyopathy is known to be associated with increased levels of inflammatory cytokines and the cell adhesion molecules. 6,7,32, 35 Inflammatory cytokines, including IL-6 and TNF-α, are known to promote LV remodeling and contractile dysfunction and play a pathogenic role in heart failure. 43, 44 Additionally, cell adhesion molecules mediate the transendothelial migration of immunocompetent cells into the cardiac tissue 33 We found that the increase in IL-6, TNF-α, PAI-1, ICAM-1, and VCAM-1 mRNA was more pronounced in CRP/DM than in Wt/DM.…”

Section: Discussionmentioning

confidence: 99%

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Overexpression of Human C-Reactive Protein Exacerbates Left Ventricular Remodeling in Diabetic Cardiomyopathy

Mano

Anzai

Kaneko

et al. 2011

Circ J

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Section: Cardiac Inflammation Ras and Bnpmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Overexpression of Human C-Reactive Protein Exacerbates Left Ventricular Remodeling in Diabetic Cardiomyopathy

Mano

Anzai

Kaneko

et al. 2011

Circ J

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“…Cardiac function and BP assay Cardiac function and BP were measured by echocardiography and tail-cuff manometry, respectively [21,22]. See ESM Methods for details.…”

Section: Methodsmentioning

confidence: 99%

Fibroblast growth factor 21 protects the heart from apoptosis in a diabetic mouse model via extracellular signal-regulated kinase 1/2-dependent signalling pathway

et al. 2015

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Aims/hypothesis This study investigated fibroblast growth factor 21 (FGF21)-mediated cardiac protection against apoptosis caused by diabetic lipotoxicity and explored the protective mechanisms involved. Methods Cardiac Fgf21 mRNA expression was examined in a diabetic mouse model using real-time PCR. After preincubation of palmitate-treated cardiac H9c2 cells and primary cardiomyocytes with FGF21 for 15 h, apoptosis and Fgf21-induced cell-survival signalling were investigated using small interfering (si)RNA and/or pharmacological inhibitors. We also examined the cardiac apoptotic signalling and structural and functional indices in wild-type and Fgf21-knockout (Fgf21-KO) diabetic mice.Results In a mouse model of type 1 diabetes, cardiac Fgf21 expression was upregulated about 40-fold at 2 months and 3-1.5-fold at 4 and 6 months after diabetes. FGF21 significantly reduced palmitate-induced cardiac apoptosis. Mechanistically, palmitate downregulated, but FGF21 upregulated, phosphorylation levels of extracellular signal-regulated kinase (ERK)1/ 2, mitogen-activated protein kinase 14 (p38 MAPK) and AMP-activated protein kinase (AMPK). Inhibition of each kinase with its inhibitor and/or siRNA revealed that FGF21 prevents palmitate-induced cardiac apoptosis via upregulating the ERK1/2-dependent p38 MAPK-AMPK signalling pathway. In vivo administration of FGF21, but not FGF21 plus ERK1/2 inhibitor, to diabetic or fatty-acid-infused mice significantly prevented cardiac apoptosis and reduced inactivation of ERK1/2, p38 MAPK and AMPK and prevented cardiac remodelling and dysfunction. The Fgf21-KO mice were more susceptible to diabetes-induced cardiac apoptosis, and this could be prevented by administration of FGF21. Deletion of Fgf21 did not further exacerbate cardiac dysfunction. Conclusions/interpretation These results demonstrate that FGF21 prevents lipid-or diabetes-induced cardiac apoptosis by activating the ERK1/2-p38 MAPK-AMPK pathway. FGF21 may be a therapeutic target for the treatment of diabetes-related cardiac damage.Electronic supplementary material The online version of this article

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“…To assess cardiac function, transthoracic echocardiography was performed in mice using a Vevo 770 HighResolution Imaging System (Visual Sonics, Toronto, ON, Canada) equipped with a high-frame rate RMV 707B Scanhead (focal length 12.7 mm, frequency 30.0 MHz), as described previously (22). The indices directly measured Levels of TNF-a and IL-6 in the cultured cell medium and mouse plasma were measured with specific ELISA kits (eBioscience, San Diego, CA) according to the manufacturer's instructions, as described in our previous publication.…”

Section: Cardiac Function Measurements By Echocardiographymentioning

confidence: 99%

Inhibition of JNK Phosphorylation by a Novel Curcumin Analog Prevents High Glucose–Induced Inflammation and Apoptosis in Cardiomyocytes and the Development of Diabetic Cardiomyopathy

Pan¹,

et al. 2014

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Hyperglycemia-induced inflammation and apoptosis have important roles in the pathogenesis of diabetic cardiomyopathy. We recently found that a novel curcumin derivative, C66, is able to reduce the high glucose (HG)-induced inflammatory response. This study was designed to investigate the protective effects on diabetic cardiomyopathy and its underlying mechanisms. Pretreatment with C66 significantly reduced HG-induced overexpression of inflammatory cytokines via inactivation of nuclear factor-κB in both H9c2 cells and neonatal cardiomyocytes. Furthermore, we showed that the inhibition of Jun NH2-terminal kinase (JNK) phosphorylation contributed to the protection of C66 from inflammation and cell apoptosis, which was validated by the use of SP600125 and dominant-negative JNK. The molecular docking and kinase activity assay confirmed direct binding of C66 to and inhibition of JNK. In mice with type 1 diabetes, the administration of C66 or SP600125 at 5 mg/kg significantly decreased the levels of plasma and cardiac tumor necrosis factor-α, accompanied by decreasing cardiac apoptosis, and, finally, improved histological abnormalities, fibrosis, and cardiac dysfunction without affecting hyperglycemia. Thus, this work demonstrated the therapeutic potential of the JNK-targeting compound C66 for the treatment of diabetic cardiomyopathy. Importantly, we indicated a critical role of JNK in diabetic heart injury, and suggested that JNK inhibition may be a feasible strategy for treating diabetic cardiomyopathy.

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Metallothionein Suppresses Angiotensin II–Induced Nicotinamide Adenine Dinucleotide Phosphate Oxidase Activation, Nitrosative Stress, Apoptosis, and Pathological Remodeling in the Diabetic Heart

Abstract: Metallothionein suppresses Ang II-induced NOX-dependent nitrosative damage and cell death in both nondiabetic and diabetic hearts early in the time course of injury and prevents the late development of Ang II-induced cardiomyopathy.

Cited by 111 publications

References 32 publications

Overexpression of Human C-Reactive Protein Exacerbates Left Ventricular Remodeling in Diabetic Cardiomyopathy

Overexpression of Human C-Reactive Protein Exacerbates Left Ventricular Remodeling in Diabetic Cardiomyopathy

Fibroblast growth factor 21 protects the heart from apoptosis in a diabetic mouse model via extracellular signal-regulated kinase 1/2-dependent signalling pathway

Inhibition of JNK Phosphorylation by a Novel Curcumin Analog Prevents High Glucose–Induced Inflammation and Apoptosis in Cardiomyocytes and the Development of Diabetic Cardiomyopathy

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