Cardioprotective effects of incretin during ischaemia-reperfusion

Chinda, Kroekkiat; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

doi:10.1177/1479164112440816

Cited by 28 publications

(26 citation statements)

References 56 publications

(146 reference statements)

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“…Taken together, these results suggested that geniposide pretreatment protected H9c2 cells against H/R-caused injury through Bcl-2/ Bax/mitochondria apoptotic pathways. GLP-1, a gut hormone, and GLP-1 analogs have beneficial effects on cardiovascular system by inhibiting cardiomyocyte apoptosis during I/R [23,[40][41][42][43]. It has been reported that geniposide, as a novel GLP-1R agonist, exerts different protective effects by activating GLP-1R in various tissues [15][16][17][18][19].…”

Section: Discussionmentioning

confidence: 99%

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Geniposide Prevents Hypoxia/Reoxygenation-Induced Apoptosis in H9c2 Cells: Improvement of Mitochondrial Dysfunction and Activation of GLP-1R and the PI3K/AKT Signaling Pathway

Jiang

Chang²,

Wang³

et al. 2016

Cell Physiol Biochem

104

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Background/Aims: Myocardial ischemia/reperfusion injury is a major cause of morbidity and mortality associated with coronary heart disease. Many studies have demonstrated that natural products are promising chemotherapeutic drugs counteracting the loss of cardiomyocytes. Thus, the purpose of the present study was to investigate the effects of geniposide, a traditional Chinese herb extract from Gardenia jasminoides J. Ellis, on cardiomyocyte apoptosis induced by hypoxia/reoxygenation (H/R) in H9c2 cells, and their underlying mechanisms. Methods: Cell viability and apoptosis ratio were assessed using the cell counting kit-8 assay and Annexin V/propidium iodide (PI) staining. The concentrations of lactate dehydrogenase (LDH), intracellular total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were detected by microplate reader. The production of reactive oxygen species/reactive nitrogen species (ROS/RNS), the level of mitochondrial calcium, and mitochondrial membrane potential depolarization were measured by confocal laser scanning microscopy. Mitochondrial morphology was visualized using transmission electron microscopy. The expressions of Bcl-2 mRNA and Caspase-3 mRNA were measured by reverse transcription-polymerase chain reaction (RT-PCR). The protein levels of cleaved caspase-3, Bcl-2, Bax, AKT, p-AKT^serine473, cytochrome-c were detected by western bloting. Results: Geniposide pretreatment increased cell viability, decreased LDH levels in the supernatant, and inhibited cardiomyocyte apoptosis caused by H/R. Furthermore, geniposide reversed mitochondrial dysfunction by decreasing oxidative stress products (ROS/RNS and MDA), increasing anti-oxidative enzyme (T-SOD) level, improving mitochondrial morphology, attenuating mitochondrial calcium overload and blunting depolarization of mitochondrial membrane. Moreover, geniposide pretreatment increased Bcl-2 level and decreased Bax level, thus enhancing the Bcl-2/Bax ratio. Consistent with the above result, Bcl-2 mRNA expression was upregulated and caspase-3 mRNA expression was downregulated by geniposide. In addition, geniposide decreased the protein expression of cleaved caspase-3 and cytochrome-c and increased the level p-AKT^serine473. The protective effects of geniposide were partially reversed by glucagon-like pepitide-1 receptor antagonist exendin-(9-39) and the phosphatidylinositol 3 kinase (PI3K) inhibitor LY294002. Conclusions: Our results suggest that geniposide pretreatment inhibits H/R-induced myocardial apoptosis by reversing mitochondrial dysfunction, an effect in part due to activation of GLP-1R and PI3K/AKT signaling pathway.

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Section: Discussionmentioning

confidence: 99%

“…2). Geniposide pretreatment (10,20,40, 80 μM) remarkably reduced the level of LDH (P < 0.05). LDH level in the 40 μM and 80 μM geniposide pretreatment groups were lower than that of 10 μM and 20 μM geniposide pretreatment groups (P < 0.05, Fig.…”

Section: Geniposide Decreased Ldh Level In H9c2 Cells Subjected To H/rmentioning

confidence: 99%

Geniposide Prevents Hypoxia/Reoxygenation-Induced Apoptosis in H9c2 Cells: Improvement of Mitochondrial Dysfunction and Activation of GLP-1R and the PI3K/AKT Signaling Pathway

Jiang

Chang²,

Wang³

et al. 2016

Cell Physiol Biochem

104

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“…Glucagon-like peptide 1 is an incretin hormone released from intestinal L-cells that causes an increased insulin secretion, decreased glucagon secretion, and improved insulin sensitivity and has been shown to exert direct cardiovascular effects in both experimental and clinical studies with or without insulin resistance (13,14). Although the glycemic control effects of dipeptidyl peptidase-4 inhibitor have been extensively studied, the roles of vildagliptin on the heart are still unclear (15,16).…”

mentioning

confidence: 99%

Cardioprotective Effects of Metformin and Vildagliptin in Adult Rats with Insulin Resistance Induced by a High-Fat Diet

et al. 2012

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Insulin resistance has been shown to be associated with cardiac sympathovagal imbalance, myocardial dysfunction, and cardiac mitochondrial dysfunction. Whereas metformin is a widely used antidiabetic drug to improve insulin resistance, vildagliptin is a novel oral antidiabetic drug in a group of dipeptidyl peptidase-4 inhibitors in which its cardiac effect is unclear. This study aimed to determine the cardiovascular effects of metformin and vildagliptin in rats with insulin resistance induced by high-fat diet. Male Wistar rats were fed with either a normal diet or high-fat diet (n =24 each) for 12 wk. Rats in each group were divided into three subgroups to receive the vehicle, metformin (30 mg/kg, twice daily), or vildagliptin (3 mg/kg, once daily) for another 21 d. Heart rate variability (HRV), cardiac function, and cardiac mitochondrial function were determined and compared among these treatment groups. Rats exposed to a high-fat diet developed increased body weight, visceral fat, plasma insulin, cholesterol, oxidative stress, depressed HRV, and cardiac mitochondrial dysfunction. Metformin and vildagliptin did not alter body weight and plasma glucose levels but decreased the plasma insulin, total cholesterol, and oxidative stress levels. Although both metformin and vildagliptin attenuated the depressed HRV, cardiac dysfunction, and cardiac mitochondrial dysfunction, vildagliptin was more effective in this prevention. Furthermore, only vildagliptin prevented cardiac mitochondrial membrane depolarization caused by consumption of a high-fat diet. We concluded that vildagliptin is more effective in preventing cardiac sympathovagal imbalance and cardiac dysfunction, as well as cardiac mitochondrial dysfunction, than metformin in rats with insulin resistance induced by high-fat diet.

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“…The effects of incretin-based therapy using glucagon-like peptide-1 receptor agonists and inhibitors of dipeptidyl peptidase-4 have been promising, but need further preclinical and clinical testing [127,128].…”

Section: Reactivation Of Endogenous Cardioprotectionmentioning

confidence: 99%

Cardiomyocyte changes in the metabolic syndrome and implications for endogeneous protective strategies

Oosterlinck

Herijgers

2014

Expert Review of Cardiovascular Therapy

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The deadly quartet of the metabolic syndrome includes obesity, impaired glucose tolerance, an atherogenic lipid profile and hypertension. The synergistic effects of these comorbidities lead to a combination of functional and structural cardiomyocyte changes and finally result in a global adverse remodeling process. Overall cardiovascular outcome is significantly impaired. Furthermore, these changes increase the need for surgical or endovascular interventions and impair their outcomes. This is potentially due to current cardioprotective techniques being insufficiently tailored to the specific needs of these patients. The following review discusses the observed cardiomyocyte changes and systemic factors contributing to these changes. It describes the ensuing problems in cardioprotection and discusses strategies that can be taken to divert or circumvent these detrimental changes.

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Cardioprotective effects of incretin during ischaemia-reperfusion

Cited by 28 publications

References 56 publications

Geniposide Prevents Hypoxia/Reoxygenation-Induced Apoptosis in H9c2 Cells: Improvement of Mitochondrial Dysfunction and Activation of GLP-1R and the PI3K/AKT Signaling Pathway

Geniposide Prevents Hypoxia/Reoxygenation-Induced Apoptosis in H9c2 Cells: Improvement of Mitochondrial Dysfunction and Activation of GLP-1R and the PI3K/AKT Signaling Pathway

Cardioprotective Effects of Metformin and Vildagliptin in Adult Rats with Insulin Resistance Induced by a High-Fat Diet

Cardiomyocyte changes in the metabolic syndrome and implications for endogeneous protective strategies

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