Cardioprotection by early metoprolol- attenuation of ischemic vs. reperfusion injury?

Kleinbongard, Petra

doi:10.1007/s00395-020-0814-2

Cited by 22 publications

(16 citation statements)

References 22 publications

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“…CHD is one of the leading causes of death worldwide with a trend to be younger, despite the remarkable progress in the research of molecular and pathological mechanisms and treatment of it [17][18][19][20][21][22][23]. Identifying risk factors and adequate management is one of the corner stones of preventing CHD.…”

Section: Discussionmentioning

confidence: 99%

High-Density Lipoprotein Cholesterol in Young Nondiabetic Coronary Heart Disease Patients

Cui

et al. 2021

Cardiology Research and Practice

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Objective. To investigate the association between the lipid profiles and coronary heart disease (CHD) in nondiabetic patients younger than 65 years of age. Method. 424 patients were enrolled in this study from January 2019 to December 2020. All the patients were screened for clinically indicated coronary angiography. They were divided into two groups according to the coronary angiography results: 340 patients with the presence of CHD (at least one coronary artery stenosis ≥50%) were classified as the CHD group, and the rest with the absence of CHD comprised the normal group. The demographic data and lipid profiles were compared. Result. CHD was higher in males than females (84.5% vs. 62.2%, P < 0.001 ). In the CHD group, the level of high‐density lipoprotein cholesterol (HDL-C) was lower P < 0.001 , while the triglyceride (TG)/HDL-C ratio was higher P = 0.022 . No significant differences were shown between the two groups in terms of age, family history of CHD, hypertension, and the levels of TC, TG, and LDL-C. Gender differences were further explored. In men, except for the level of HDL-C which was significantly lower in the CHD group than that in the normal group P = 0.017 , parameters were comparable. A binary logistic regression model further indicated that HDL-C was associated with CHD (OR = 0.137, 95%CI: 0.031–0.594, P = 0.008 ). Also, with the increase of the number of coronary artery with lesions, the levels of HDL-C decreased significantly in men. In women, no differences were observed between the CHD group and normal group. Conclusion. HDL-C may be inversely associated with the risk of CHD in young nondiabetes patients, especially in men. More research is needed to confirm it.

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Section: Discussionmentioning

confidence: 99%

High-Density Lipoprotein Cholesterol in Young Nondiabetic Coronary Heart Disease Patients

Cui

et al. 2021

Cardiology Research and Practice

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“…Finally, we also report that Opa1-mediated mitophagy is an upstream trigger of the MAPK/ERK pathway in cardiomyocytes. This is in line with previous studies, conducted in aged parkinsonian mice [71][72][73], in a murine model of sleep apnea [74], and in a model of doxorubicin-induced cardiotoxicity [75] that highlighted the relationship between mitophagy and the ERK signaling pathway. Considering the necessary role played by ERK in regulating cardiomyocyte metabolism and ATP generation, mitophagy-induced ERK activation appears as a critical mechanism to support mitochondrial metabolism and oxidative phosphorylation under hypoxic conditions.…”

Section: Discussionsupporting

confidence: 92%

Protective Effect of Optic Atrophy 1 on Cardiomyocyte Oxidative Stress: Roles of Mitophagy, Mitochondrial Fission, and MAPK/ERK Signaling

Wang

Han

et al. 2021

Oxidative Medicine and Cellular Longevity

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Myocardial infarction is associated with oxidative stress and mitochondrial damage. However, the regulatory mechanisms underlying cardiomyocyte oxidative stress during myocardial infarction are not fully understood. In the present study, we explored the cardioprotective action of optic atrophy 1- (Opa1-) mediated mitochondrial autophagy (mitophagy) in oxidative stress-challenged cardiomyocytes, with a focus on mitochondrial homeostasis and the MAPK/ERK pathway. Our results demonstrated that overexpression of Opa1 in cultured rat H9C2 cardiomyocytes, a procedure that stimulates mitophagy, attenuates oxidative stress and increases cellular antioxidant capacity. Activation of Opa1-mediated mitophagy suppressed cardiomyocyte apoptosis by downregulating Bax, caspase-9, and caspase-12 and upregulating Bcl-2 and c-IAP. Using mitochondrial tracker staining and a reactive oxygen species indicator, our assays showed that Opa1-mediated mitophagy attenuated mitochondrial fission and reduced ROS production in cardiomyocytes. In addition, we found that inhibition of the MAPK/ERK pathway abolished the antioxidant action of Opa1-mediated mitophagy in these cells. Taken together, our data demonstrate that Opa1-mediated mitophagy protects cardiomyocytes against oxidative stress damage through inhibition of mitochondrial fission and activation of MAPK/ERK signaling. These findings reveal a critical role for Opa1 in the modulation of cardiomyocyte redox balance and suggest a potential target for the treatment of myocardial infarction.

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“…Acute myocardial infarction (AMI) refers to a clinical or pathological event with evidence of myocardial injury due to acute myocardial ischemia ( Heusch, 2019 ; Kohlhauer et al, 2019 ). Although early coronary intervention and bypass surgery reduce the immediate mortality of patients, the incidence of long-term heart failure and recurrent myocardial infarction has still been increasing over time, creating a major disease burden to people worldwide ( Hausenloy et al, 2020 ; Kleinbongard, 2020 ). Studies have shown that endothelial cells are affected earlier and are more sensitive to heart ischemia injury than cardiomyocytes ( Singh et al, 2020 ; Wang et al, 2020a ).…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Overexpression of SERCA2a Alleviates Cardiac Microvascular Ischemic Injury by Suppressing Mfn2-Mediated ER/Mitochondrial Calcium Tethering

Tian

Zhang

2021

Front. Cell Dev. Biol.

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Our previous research has shown that type-2a Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) undergoes posttranscriptional oxidative modifications in cardiac microvascular endothelial cells (CMECs) in the context of excessive cardiac oxidative injury. However, whether SERCA2a inactivity induces cytosolic Ca2+ imbalance in mitochondrial homeostasis is far from clear. Mitofusin2 (Mfn2) is well known as an important protein involved in endoplasmic reticulum (ER)/mitochondrial Ca2+ tethering and the regulation of mitochondrial quality. Therefore, the aim of our study was to elucidate the specific mechanism of SERCA2a-mediated Ca2+ overload in the mitochondria via Mfn2 tethering and the survival rate of the heart under conditions of cardiac microvascular ischemic injury. In vitro, CMECs extracted from mice were subjected to 6 h of hypoxic injury to mimic ischemic heart injury. C57-WT and Mfn2KO mice were subjected to a 1 h ischemia procedure via ligation of the left anterior descending branch to establish an in vivo cardiac ischemic injury model. TTC staining, immunohistochemistry and echocardiography were used to assess the myocardial infarct size, microvascular damage, and heart function. In vitro, ischemic injury induced irreversible oxidative modification of SERCA2a, including sulfonylation at cysteine 674 and nitration at tyrosine 294/295, and inactivation of SERCA2a, which initiated calcium overload. In addition, ischemic injury-triggered [Ca2+]c overload and subsequent [Ca2+]m overload led to mPTP opening and ΔΨm dissipation compared with the control. Furthermore, ablation of Mfn2 alleviated SERCA2a-induced mitochondrial calcium overload and subsequent mito-apoptosis in the context of CMEC hypoxic injury. In vivo, compared with that in wild-type mice, the myocardial infarct size in Mfn2KO mice was significantly decreased. In addition, the findings revealed that Mfn2KO mice had better heart contractile function, decreased myocardial infarction indicators, and improved mitochondrial morphology. Taken together, the results of our study suggested that SERCA2a-dependent [Ca2+]c overload led to mitochondrial dysfunction and activation of Mfn2-mediated [Ca2+]m overload. Overexpression of SERCA2a or ablation of Mfn2 expression mitigated mitochondrial morphological and functional damage by modifying the SERCA2a/Ca2+-Mfn2 pathway. Overall, these pathways are promising therapeutic targets for acute cardiac microvascular ischemic injury.

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Cardioprotection by early metoprolol- attenuation of ischemic vs. reperfusion injury?

Cited by 22 publications

References 22 publications

High-Density Lipoprotein Cholesterol in Young Nondiabetic Coronary Heart Disease Patients

High-Density Lipoprotein Cholesterol in Young Nondiabetic Coronary Heart Disease Patients

Protective Effect of Optic Atrophy 1 on Cardiomyocyte Oxidative Stress: Roles of Mitophagy, Mitochondrial Fission, and MAPK/ERK Signaling

RETRACTED: Overexpression of SERCA2a Alleviates Cardiac Microvascular Ischemic Injury by Suppressing Mfn2-Mediated ER/Mitochondrial Calcium Tethering

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