Impact of Hyperglycemic Control on Left Ventricular Myocardium  A Molecular and Cellular Basic Study in a Diabetic Rat Model

Sung, Pei‐Hsun; Sun, Cheuk‐Kwan; Ko, Sheung‐Fat; Chang, Li-Teh; Sheu, Jiunn‐Jye; Lee, Fan-Yen; Wu, Chiung‐Jen; Chua, Sarah; Yip, Hon‐Kan

doi:10.1536/ihj.50.191

Cited by 8 publications

(10 citation statements)

References 37 publications

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“…The obese mice in the current study also exhibited the majority of these atherosclerotic risk factors. A previous study showed that poor DM control impaired LVEF [27]. However, the results of our study did not support the finding of poor DM control that ultimately impaired the LVEF function.…”

Section: Discussioncontrasting

confidence: 99%

“…Importantly, these biomarkers were remarkably decreased following reduction in obesity. Enhanced inflammatory reaction and oxidative stress are associated with myocardial damage and deterioration of heart function [27,35]. Our findings could at least partially explain why LV function was impaired in obese mice and restored in obese mice after weight reduction.…”

Section: Discussionmentioning

confidence: 65%

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Effect of obesity reduction on preservation of heart function and attenuation of left ventricular remodeling, oxidative stress and inflammation in obese mice

et al. 2012

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BackgroundObesity is an important cardiovascular risk factor. This study tested the effect of obesity reduction on preserving left ventricular ejection fraction (LVEF) and attenuating inflammation, oxidative stress and LV remodeling in obese mice.Methods and resultsEight-week-old C57BL/6 J mice (n=24) were equally divided into control (fed a control diet for 22 weeks), obesity (high-fat diet, 22 weeks), and obese reduction (OR) (high-fat diet, 14 weeks; then control diet, 8 weeks). Animals were sacrificed at post 22-week high-fat diet and the LV myocardium collected. Heart weight, body weight, abdominal-fat weight, total cholesterol level and fasting blood glucose were higher in obesity than in control and OR (all p<0.001). Inflammation measured by mRNA expressions of IL-6, MMP-9, PAI-1 and leptin and protein expression of NF-κB was higher, whereas anti-inflammation measured by mRNA expressions of adiponectin and INF-γ was lower in obesity than in control and OR (all p<0.003). Oxidative protein expressions of NOX-1, NOX-2 and oxidized protein were higher, whereas expression of anti-oxidant markers HO-1 and NQO-1 were lower (all p<0.01); and apoptosis measured by Bax and caspase 3 was higher, whereas anti-apoptotic Bcl-2 was lower in obesity as compared with control and OR (all p<0.001). The expressions of fibrotic markers phosphorylated Smad3 and TGF-β were higher, whereas expression of anti-fibrotic phosphorylated Smad1/5 and BMP-2 were lower (all p<0.02); and LVEF was lower, whereas the LV remodeling was higher in obesity than in control and OR (all p<0.001).ConclusionImpaired LVEF, enhanced LV remodeling, inflammation, fibrosis, oxidative stress and apoptosis were reversed by reduction in mouse obesity.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 65%

Effect of obesity reduction on preservation of heart function and attenuation of left ventricular remodeling, oxidative stress and inflammation in obese mice

et al. 2012

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“…To assess the role of DPP4 D and sitagliptin therapy in ROS expression in IR region of LV myocardium, the fluorescent intensity was quantified using H 2 DCFDA labeling of the myocardium as described in our previous study [ 25 ]. As expected, the relative fluorescence intensity was significantly increased in WT-IR than in other groups, significantly elevated in WT-IR-Sita and DPP4 D -IR groups than in WT-SC and DPP4 D -SC groups, but it showed no difference between the former two groups or between the latter two groups (Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…For determining the fluorescent intensity of ROS in myocardium, four additional animals were utilized in each study group. The protocol and detailed procedure of this test were based on our previous report [ 25 ]. By the end of study period (i.e., at 72 h after IR procedure), 2′,7′-dichlorodihydrofluorescin diacetate (H 2 DCFDA, Molecular Probes) was dissolved in DMSO at a concentration of 25 mg/mL.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of dipeptidyl peptidase-IV enzyme activity protects against myocardial ischemia-reperfusion injury in rats

et al. 2014

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BackgroundWe investigated whether attenuating dipeptidyl peptidase-IV (DPP4) enzyme activity protected rat heart from ischemia-reperfusion (IR) injury (40-min left anterior descending coronary artery ligation followed by 72 h reperfusion).Methods and resultsAdult male Fischer 344 rats (n = 24) were equally divided into sham-control (WT-SC), WT-IR, and WT-IR-Sita (oral sitagliptin 400 mg/kg/day for 3 days) groups, whereas adult male DPP4-deficiency (DPP4D) rats (n = 16) were equally divided into DPP4D-SC and DPP4D-IR groups. Animals were sacrificed at 72 h after reperfusion with collection of heart specimens. Infarct area (H&E), collagen deposition (Sirius-red stain), fibrotic area (Masson's trichrome), and fluorescent-ROS intensity (H2DCFDA-labeling myocardium) of left ventricle were significantly higher in WT-IR than those in other groups, significantly higher in WT-IR-Sita and DPP4D-IR groups than in WT-SC and DPP4D-SC groups (all p < 0.001), but there was no difference between the latter two groups. Protein expressions of oxidative stress (oxidized protein), reactive oxygen species (NOX-1, NOX-2), inflammation (TNF-α, NF-κB, MMP-9, VCAM-1), apoptosis (mitochondrial Bax, cleaved caspase-3 and PARP), myocardial damage markers (cytosolic cytochrome-C, γ-H2AX), and number of inflammatory cells (CD14+, CD68+, CD40+ cells) showed a pattern identical to that of histological changes among all groups (all p < 0.005), whereas markers of anti-apoptosis (Bcl-2) and mitochondrial integrity (mitochondrial cytochrome-C) as well as left ventricular ejection fraction showed an opposite pattern (all p < 0.001). Protein expressions of anti-oxidants (HO-1, NQO-1), angiogenesis factors (SDF-1α, CXCR4), and glycogen-like-peptide-1-receptor were significantly higher inWT-IR-Sita and DPP4D-IR than those in other groups (all p < 0.001).ConclusionAbrogation of DPP4 activity protects against myocardial IR injury and preserved heart function.

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“…After four weeks, the myocardial mitochondria of DM mouse began to swell and denature [12]; On days 7, 14, and 21 after a single dose of STZ (150 mg/kg) treatment, the number of TUNEL-positive cells and the amount of caspase-3 activation increased [13]; Twenty-eight days after successful modeling (STZ treatment, 60 mg/kg), cardiac apoptosis in the Sprague Dawley(SD) rats were observed to have increased (P < 0.01) [14] ; The number of cardiac myocytes,which cultured by different blood glucose level, associated with blood glucose concentration; and Hyperglycemia through mitochondrial pathway resulted in myocardial apoptosis [15]. Our previous work has indicated that, even though the expression of cleaved-caspase-3 increased, in addition to cell shrinkage and nuclear condensation in the DM-7-day group in comparison to the WT group , this increase was not statistically significant (P > 0.05), which is consistent with our reported experimental data.…”

Section: Discussionmentioning

confidence: 99%

Uncoupling protein 2 regulates myocardial apoptosis via the diabetogenic action of streptozotocin

Li¹,

Tan²,

Lü³

2011

JBiSE

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Objective: Determine the role of uncoupling protein 2 (UCP2) in the myocardial apoptosis of diabetic mellitus（DM）. Methods: DM animal models were induced by streptozotocinon (STZ) on UCP2 knock-out mice (UCP2KO) and wild-type mice (WT), which were reared for 7 and 28 days after successful modeling, respectively. The expressions of relative protein for myocardial apoptosis, pro-caspase-9, were investigated using western blot. However, the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) was used to explain apoptosis at the DNA level. Results: Image analysis showed that the expression of pro-caspase-9 protein levels increased slightly in UCP-/- + DM-7-day group comparing with DM-7-day group (P > 0.05). The expression of pro-caspase-9 protein levels increased significantly (P < 0.05）in UCP-/- + DM-28-day group comparing with DM-28-day group. TUNEL analysis indicated that UCP2 reduced the number of apoptotic myocytes in the DM-28-day group by 70% in comparison to DM-7-day group by 30% (P < 0.05). Conclusion UCP2 may be one of the most important factors that contribute to the myocardial apoptosis of DM

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Impact of Hyperglycemic Control on Left Ventricular Myocardium A Molecular and Cellular Basic Study in a Diabetic Rat Model

Cited by 8 publications

References 37 publications

Effect of obesity reduction on preservation of heart function and attenuation of left ventricular remodeling, oxidative stress and inflammation in obese mice

Effect of obesity reduction on preservation of heart function and attenuation of left ventricular remodeling, oxidative stress and inflammation in obese mice

Inhibition of dipeptidyl peptidase-IV enzyme activity protects against myocardial ischemia-reperfusion injury in rats

Uncoupling protein 2 regulates myocardial apoptosis via the diabetogenic action of streptozotocin

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