Hypercholesterolemia abrogates the protective effect of ischemic postconditioning by induction of apoptosis and impairment of activation of reperfusion injury salvage kinase pathway

Wu, Nan; Zhang, Xiaowen; Jia, Pengyu; Jia, Dalin

doi:10.1016/j.bbrc.2015.01.084

Cited by 17 publications

(25 citation statements)

References 26 publications

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“…Similar to our study, it has been shown that the cardioprotective effects of IPost in declining IS are abolished in disease conditions such as diabetes (Badalzadeh et al, 2012), metabolic syndrome (Wagner et al, 2008), and hypercholesterolemia (Wu et al, 2015b). In line with our findings, it has been reported that in disease states, loss of IPost cardioprotection can be restored by the concomitant administration of specific inhibitors including iNOS inhibitors (Badalzadeh et al, 2012;Zaman et al, 2014).…”

Section: Discussionsupporting

confidence: 93%

Ischemic postconditioning provides cardioprotective and antiapoptotic effects against ischemia–reperfusion injury through iNOS inhibition in hyperthyroid rats

Zaman

Jeddi

Daneshpour

et al. 2015

Gene

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Section: Discussionsupporting

confidence: 93%

Ischemic postconditioning provides cardioprotective and antiapoptotic effects against ischemia–reperfusion injury through iNOS inhibition in hyperthyroid rats

Zaman

Jeddi

Daneshpour

et al. 2015

Gene

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“…Despite the cellular mechanisms of hyperlipidemia influencing the conditioning cardioprotection is unclear, but hypercholesterolemia-induced deterioration of RISK pathway can provide reference to elaborate the mechanisms. A study performed by Wu et al (56) showed that hypercholesterolemia inhibited the phosphorylation of Akt and ERK1/2, and subsequently induced excessive apoptosis by down-regulating Bcl-2 and up-regulating Bax,…”

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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“…11 studies (4,13,21,27,29,31,35,40,41,43) involved the effects of IPC on myocardium apoptosis index. The analysis showed that IPC reduced apoptosis level significantly (SMD -2.56, 95% CI -3.56 to -1.55, P<0.00001), and overall study heterogeneity was high (78%) ( Figure 5).…”

Section: Apoptosis Indexmentioning

confidence: 99%

“…According to several relevant studies, IPC seems to lose its cardioprotective effect in subjects with diabetes and hyperlipidemia, while the underlying mechanism is largely unknown. At present, the accumulation of ROS led by aggravated oxidative stress is thought to account for the inefficiency of IPC in diabetes and hyperlipidemia rats models (4,6,8,42,43).…”

mentioning

confidence: 99%

“…The outcomes in diabetic rat models were consistent with each other primarily, but the data from studies of hyperlipidemia rat models appeared discordantly. Outcomes from 2 of the studies (9,43) showed that IPC was positive in protecting myocardium from IR injury in hyperlipidemia rat models, as well as in the rat models without pre-existing disease. Another 2 studies (7,8) implied that the protective effect of IPC was abolished in hyperlipidemia rat models.…”

mentioning

confidence: 99%

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The Protective Effects of Myocardial Ischemic Postconditioning on Cardiac Surgry: A Systematic Review and Meta-Analysis of Rats and Clinical Trials

Zhou¹,

Xia²,

Guo³

2015

J Anesth Perioper Med

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Background: Ischemic postconditioning (IPC) is a potent protective strategy implemented in animal myocardial ischemic-reperfusion (IR) models, while it has not yet been translated universally into clinical practice. We performed a unique systematic review and meta-analysis of animal and clinical studies respectively, to assess the protective effects of myocardial IPC and provide a new perspective for clinical practice. Methods: PubMed and Web of Science were searched for relevant researches. Trials met our inclusion criteria were selected and reviewed, and the meta-analyses were performed via Review Manager. Results: 44 trials were included in the meta-analysis. In animal studies, IPC demonstrated a decrease in size of myocardial infarction (standardized mean difference [SMD] -3.21, 95% confidence interval [CI] -3.89 to -2.52, P<0.00001), however, subgroup analysis showed that the protective effects of IPC disappeared in diabetic rats and hyperlipidemia rats (SMD -0.10, 95% CI -1.32 to 1.12, P=0.05; SMD -2.02, 95% CI -4.29 to 0.26, P=0.08, respectively). IPC reduced apoptosis index significantly (SMD -2.56, 95% CI -3.56 to -1.55, P<0.00001), while subgroup analysis indicted that IPC had no effect on decrease in level of myocardium apoptosis in hyperlipidemia rats (SMD -0.31, 95% CI -1.13 to 0.50, P=0.46). In clinical trials, no differences were noted in mortality between IPC and IR patients (SMD 0.44, 95% CI 0.07 to 2.85, P=0.41). IPC decreased the level of cardiac troponin I (cTnI) (SMD -1.74, 95% CI -2.71 to -0.78, P=0.0004), reduced the inotrope score (SMD -2.31, 95% CI -2.85 to -1.76, P<0.00001), shortened the time of ventilation and intensive care unit (ICU) stay (SMD -0.57, 95% CI -0.87 to -0.26, P=0.0002; SMD -0.57, 95% CI -0.84 to -0.30, P<0.0001, respectively). Conclusions: Myocardial IPC provided efficient protective effects for healthy rats rather than diabetic or hyperlipidemia rats. In clinical trials, IPC appeared to be beneficial to cardiac function and cardiac surgery prognosis, but had no effect on postoperative cardiac death.

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Hypercholesterolemia abrogates the protective effect of ischemic postconditioning by induction of apoptosis and impairment of activation of reperfusion injury salvage kinase pathway

Cited by 17 publications

References 26 publications

Ischemic postconditioning provides cardioprotective and antiapoptotic effects against ischemia–reperfusion injury through iNOS inhibition in hyperthyroid rats

Ischemic postconditioning provides cardioprotective and antiapoptotic effects against ischemia–reperfusion injury through iNOS inhibition in hyperthyroid rats

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

The Protective Effects of Myocardial Ischemic Postconditioning on Cardiac Surgry: A Systematic Review and Meta-Analysis of Rats and Clinical Trials

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