Hypercholesterolemia blocked sevoflurane-induced cardioprotection against ischemia–reperfusion injury by alteration of the MG53/RISK/GSK3β signaling

Ma, Liang; Zhang, Fengjiang; Qian, Ling-Bo; Kong, Fanhua; Sun, Junfeng; Zhou, Cheng; Peng, Yunan; Xu, Hao; Wang, Wenna; Wen, Chuan-Yun; Zhu, Manhua; Chen, Gang; Lu, Yu; Liu, Xianbao; Wang, Jianan; Yan, Min

doi:10.1016/j.ijcard.2013.06.037

Cited by 40 publications

(41 citation statements)

References 32 publications

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“…For example, Prasan et al (14) demonstrated that NO production is decreased in the hearts of hypercholesterolemic rabbits during I/R, and Schwemmer et al (29) detected decreased cGMP levels in the hearts of hypercholesterolemic guinea pigs. Furthermore, previous studies have also demonstrated that cardioprotective mechanisms, such as preconditioning and postconditioning, in which the NO/sGC pathway has an important role, are abolished in hyperlipidemia (16)(17)(18). Therefore, we hypothesize that NO donors may have induced cardioprotection against I/R injury in hypercholesterolemic hearts.…”

Section: Discussionmentioning

confidence: 70%

“…The high-cholesterol diet consisted of 1.5% cholesterol, 5% egg yolk powder, 10% lard, 0.5% sodium cholate, 3% sugar and 80% normal feed (Beijing Keao Xieli Feed Co., Ltd., Beijing, China). Wistar rats were selected for the present study because they had previously demonstrated a moderate increase in serum cholesterol level after receiving a high-cholesterol diet, without developing substantial atherosclerosis (18). The normocholesterolemic group contained fewer animals as it was set up to determine that the hypercholesterolemia model was successfully established.…”

Section: Induction Of Experimental Hypercholesterolemiamentioning

confidence: 99%

“…Previous studies have demonstrated that this vulnerability may be associated with the following: Increased expression of proapoptotic proteins, decreased expression of prosurvival proteins, increased myocardial inflammatory responses and oxidative/nitrative stress, inhibition of nitric oxide (NO) synthesis, and the impaired opening of mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels, in response to myocardial I/R (10-15). Furthermore, hypercholesterolemia abrogates the cardioprotection afforded by IPC, IPost and specific pharmacological agents, such as sevoflurane (16)(17)(18), however the exact underlying mechanisms are yet to be fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacological preconditioning and postconditioning with nicorandil attenuates ischemia/reperfusion-induced myocardial necrosis and apoptosis in hypercholesterolemic rats

Shu

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Pharmacological preconditioning and postconditioning may reduce myocardial necrosis and apoptosis during ischemia/reperfusion (I/R), however, hypercholesterolemia interferes with the associated cardioprotective mechanisms. The present study investigated whether pharmacological preconditioning and postconditioning with nicorandil could attenuate myocardial necrosis and apoptosis induced by I/R in hypercholesterolemic rats, and explored the possible mechanisms involved. Male Wistar rats (n=160) were fed normal (normocholesterolemic group, n=10) or high-cholesterol (hypercholesterolemic group, n=150) diets for 8 weeks. Hearts harvested from the normal and hypercholesterolemic rats were subsequently placed on modified Langendorff perfusion apparatus and 30-min global ischemia was performed, followed by 120-min reperfusion. Nicorandil (1, 3, 10, 30, 100 µmol/l), and mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channel blocker 5-hydroxydecanoic acid sodium salt (5-HD) (100 µmol/l) or soluble guanylyl cyclase (sGC) blocker 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 µmol/l) were perfused for 10 min, prior to ischemia or at the onset of reperfusion. The myocardial infarct size was determined by triphenyltetrazolium chloride staining, and cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. In order to investigate the potential mechanisms, the expression levels of caspase-3, B-cell lymphoma-2 (Bcl-2) proteins and Bcl-2-associated X protein (Bax) were measured using western blot analysis. The present study demonstrated that, in hypercholesterolemic rats, pharmacological preconditioning and postconditioning with nicorandil decreased I/R-induced myocardial necrosis and apoptosis in a concentration-dependent manner. The optimal preconditioning and postconditioning concentration of nicorandil determined to have anti-infarct and anti-apoptosis effects was 30 µmol/l, which significantly (P<0.05) reduced the infarct size to 14.88±3.25% and 15.96±3.29%, and attenuated the percentage of cardiomyocyte apoptosis to 25.20±3.93% and 26.18±4.82%, respectively, compared with the I/R group. However, the cardioprotective effects of nicorandil were partially suppressed by cotreatment with 5-HD or ODQ. Western blot analysis demonstrated that pharmacological preconditioning and postconditioning with nicorandil significantly downregulated caspase-3 and Bax expression, and upregulated Bcl-2 expression compared with the I/R group (P<0.05). The results of the present study suggest that pharmacological preconditioning and postconditioning with nicorandil may protect hypercholesterolemic hearts against I/R-induced necrosis and apoptosis; and the cardioprotective effects of nicorandil may be due to the dual pharmacological mechanisms of opening the mitoKATP channels and a nitric oxide/sGC-dependent mechanism, and regulation of the expression of caspase-3, Bax and Bcl-2.

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Section: Discussionmentioning

confidence: 70%

Section: Induction Of Experimental Hypercholesterolemiamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pharmacological preconditioning and postconditioning with nicorandil attenuates ischemia/reperfusion-induced myocardial necrosis and apoptosis in hypercholesterolemic rats

Shu

et al. 2015

Experimental and Therapeutic Medicine

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“…RISK pathway (21)(22)(23) (Figure 2). It will provide a novel cardioprotective therapeutic strategy for the treatment of acute myocardial infarction.…”

Section: Reperfusion Injury Salvage Kinase Pathwaymentioning

confidence: 99%

“…Recent studies have demonstrated that hyperchoesterolemia abrogated sevoflurane or ischemic-induced cardioprotection by alteration of upstream signaling of GSK3β, while it was reversed by GSK3β inhibitor SB216763. Furthermore, investigators showed that MG53, an upstream signaling cascade of Akt, contributed to acute membrane repair in cardiomyocytes and was impaired in hypercholesterolemic rat hearts, which was responsible for the deficit of Akt and ERK1/2 phosphorylation (22,59). It will provide a new target for restoring the conditioning protection in hypercholesterolemic hearts.…”

Section: Hyperlipidemia and Hypercholesterolemiamentioning

confidence: 99%

Impaired RISK-GSK3β Pathway is Responsible for Comorbidities by Suppressing the Conditioning Cardioprotection

Jin¹,

Zhang²

2016

J Anesth Perioper Med

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Aim of review:This review elaborates the role of reperfusion injury salvage kinase and glycogen synthase kinase 3β (RISK-GSK3β) pathway in myocardial ischemia/reperfusion injury (IRI) and whether its impairment is responsible for comorbidities due to the suppression of the conditioning cardioprotection. Method: We review the articles about RISK-GSK3β pathway in myocardial IRI published in the last two decades. Recent findings: The RISK, including phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and extracellular signal regulated kinase 1/2 (ERK1/2), combines with the downstream target of GSK3β, which confers important role in the conditioning cardioprotection when activated specifically at the time of myocardial reperfusion. Unfortunately, the conditioning protection is weakened or abolished when equipped with comorbidities such as aging, diabetes, obesity, as well as heart diseases. It has been speculated that the pathological processes resulting in RISK-GSK3β pathway alterations may affect the development of IRI and the responses to conditioning. Summary: The impairment of RISK-GSK3β pathway is responsible for the reduction of conditioning cardioprotection and any strategy that repairs the impairment may have the potential to restore the conditioning against the IRI in the heart in the state of comorbidities.

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Luteolin alleviates cardiac ischemia/reperfusion injury in the hypercholesterolemic rat via activating Akt/Nrf2 signaling

Yang

Wang

Zhou

et al. 2018

Naunyn-Schmiedeberg's Arch Pharmacol

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Myocardial ischemia/reperfusion (I/R) injury in hypercholesterolemia is associated with oxidative stress, while luteolin is known to reduce oxidative stress by activating Akt/nuclear factor erythroid-2-related factor 2 (Nrf2) signaling and alleviate cardiac I/R injury. Here, we investigated whether luteolin pretreatment diminishes myocardial I/R injury in hypercholesterolemic rats by activating Akt/Nrf2 signaling. Hypercholesterolemic rats were produced by 2% cholesterol diet for 8 weeks. Luteolin (100 mg/kg/day, i.g.) or LY294002 was administered for the last 2 weeks. The hearts were then isolated and subjected to 30 min of global ischemia followed by 120 min of reperfusion. Pretreatment with luteolin significantly improved left ventricular function throughout reperfusion, increased cardiac tissue viability, reduced coronary lactate dehydrogenase release and the myocardial malondialdehyde level, upregulated p-Akt and p-GSK3β expressions, inhibited nuclear translocation of Fyn, and activated Nrf2 function in hypercholesterolemic I/R rat hearts. All these improving effects of luteolin were significantly attenuated by LY294002. Ca-induced mitochondrial permeability transition pore (mPTP) opening and mitochondrial inner membrane potential reduction were significantly inhibited in ventricular myocytes isolated from luteolin-treated hypercholesterolemic rats, which were attenuated by LY294002. These results indicate that luteolin protects the hypercholesterolemic heart against I/R injury due to upregulation of Akt-mediated Nrf2 antioxidative function and inhibition of mPTP.

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Hypercholesterolemia blocked sevoflurane-induced cardioprotection against ischemia–reperfusion injury by alteration of the MG53/RISK/GSK3β signaling

Cited by 40 publications

References 32 publications

Pharmacological preconditioning and postconditioning with nicorandil attenuates ischemia/reperfusion-induced myocardial necrosis and apoptosis in hypercholesterolemic rats

Pharmacological preconditioning and postconditioning with nicorandil attenuates ischemia/reperfusion-induced myocardial necrosis and apoptosis in hypercholesterolemic rats

Impaired RISK-GSK3β Pathway is Responsible for Comorbidities by Suppressing the Conditioning Cardioprotection

Luteolin alleviates cardiac ischemia/reperfusion injury in the hypercholesterolemic rat via activating Akt/Nrf2 signaling

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