Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

Bøtker, Hans Erik; Hausenloy, Derek J.; Andreadou, Ioanna; Antonucci, Salvatore; Boengler, Kerstin; Davidson, Sean M.; Deshwal, Soni; Devaux, Yvan; Lisa, Fabio Di; Sante, Moises Di; Efentakis, Panagiotis; Femminò, Saveria; Garcı́a-Dorado, David; Giricz, Zoltán; Ibáñez, Borja; Iliodromitis, Efstathios K.; Kaludercic, Nina; Kleinbongard, Petra; Neuhäuser, Markus; Ovize, Michel; Pagliaro, Pasquale; Rahbek-Schmidt, Michael; Ruiz‐Meana, Marisol; Schlüter, Klaus‐Dieter; Schulz, Rainer; Skyschally, Andreas; Wilder, Catherine D. E.; Yellon, Derek M.; Ferdinándy, Péter; Heusch, Gerd

doi:10.1007/s00395-018-0696-8

Cited by 322 publications

(299 citation statements)

References 465 publications

(694 reference statements)

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“…The microglia BV‐2 cell line was obtained from the ATCC (Rockefeller) and cultured in a humidified incubator maintained in 5% CO 2 at 37°C and in DMEM/F12 (1:1) supplemented with 0.005 mg/ml insulin, 0.005 mg/ml transferrin, 0.005 mg/ml selenium, 10% (vol/vol) fetal bovine serum (FBS), and 40 ng/ml dexamethasone (Gibco, CA; Linkermann, ; Magni et al, ). To establish the in vitro model, BV‐2 cells were treated with LPS (Sigma‐Aldrich) as described previously (Bocci et al, ; Botker et al, ).…”

Section: Methodsmentioning

confidence: 99%

MKP1 reduces neuroinflammation via inhibiting endoplasmic reticulum stress and mitochondrial dysfunction

Huang

Jiang

2019

Journal Cellular Physiology

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MAP kinase phosphatase 1 (MKP1) has been identified as an antiapoptotic protein via sustaining mitochondrial function. However, the role of MKP1 in neuroinflammation has not been fully understood. The aim of this study is to figure out the influence of MKP1 in lipopolysaccharide (LPS)-treated microglia BV-2 cells and investigate whether MKP1 reduces BV-2 cell death via modulating endoplasmic reticulum (ER) stress and mitochondrial dysfunction. The results of this study demonstrated that MKP1 was rapidly downregulated after exposure to LPS. However, the transfection of MKP1 adenovirus could reverse cell viability and attenuate LPS-mediated BV-2 cell apoptosis. Mechanistically, MKP1 overexpression alleviated ER stress and corrected LPS-induced calcium overloading. Besides, MKP1 adenovirus transfection also reversed mitochondrial bioenergetics, maintained mitochondrial membrane potential, and blocked mitochondria-initiated apoptosis signals. Furthermore, we found that MKP1 overexpression is associated with inactivation of mitogen-activated protein kinase-c-Jun N-terminal kinase (MAPK-JNK) pathway. Interestingly, the activation of MAPK-JNK pathway could abolish the protective effects of MKP1 on BV-2 cells survival and mitochondrial function in the presence of LPS. Altogether, our results identified MKP1 as a primary defender of neuroinflammation via modulating ER stress and mitochondrial function in a manner dependent on MAPK-JNK pathway. These findings may open a new window for the treatment of neuroinflammation in the clinical setting. K E Y W O R D S BV-2 cells, ER stress, LPS, mitochondrial damage, MKP1, neuroinflammation

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Section: Methodsmentioning

confidence: 99%

MKP1 reduces neuroinflammation via inhibiting endoplasmic reticulum stress and mitochondrial dysfunction

Huang

Jiang

2019

Journal Cellular Physiology

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“…It is involved in various conditions such as inflammatory disease (Abeysuriya, Lockley, Robinson, & Postnova, ), fibrotic disease (Angelova et al, ), and multiple cancers (Batista & Helguero, ). Recent studies (Araki et al, ; Botker et al, ) suggested that this pathway also relates to the development of AS (Afonso et al, ). In addition, it participates in the response to inflammation, which may cause ED (Ba & Boldogh, ; Brazao et al, ).…”

Section: Introductionmentioning

confidence: 99%

PTEN inhibition attenuates endothelial cell apoptosis in coronary heart disease via modulating the AMPK–CREB–Mfn2‐mitophagy signaling pathway

Wang

Zhao

et al. 2019

Journal Cellular Physiology

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Atherosclerosis (AS) is a major pathogenic factor in patients with cardiovascular diseases, and endothelial dysfunction (ED) plays a primary role in the occurrence and development of AS. In our study, we attempted to evaluate the role of phosphatase and tensin homolog (PTEN) in endothelial cell apoptosis under oxidized low-density lipoprotein (ox-LDL) stimulation and identify the associated mechanisms. The results of our study demonstrated that ox-LDL induced human umbilical vein endothelial cell (HUVEC) death via mitochondrial apoptosis, as evidenced by reduced mitochondrial potential, increased mitochondria permeability transition pore opening, cellular calcium overload, and caspase-9/-3 activation. In addition, ox-LDL also suppressed cellular energy production via downregulating the mitochondrial respiratory complex. Moreover, ox-LDL impaired HUVECs migration. Western blot analysis showed that PTEN expression was upregulated after exposure to ox-LDL and knockdown of PTEN could attenuate ox-LDL-mediated endothelial cell damage. Furthermore, we found that ox-LDL impaired mitophagy activity, whereas PTEN deletion could improve mitophagic flux and this effect relied on the activity of the AMPactivated protein kinase (AMPK)-cAMP-response element-binding protein (CREB)-Mitofusin-2 (Mfn2) axis. When the AMPK-CREB-Mfn2 pathway was inhibited, PTEN deletion-associated HUVECs protection was significantly reduced, suggesting that the AMPK-CREB-Mfn2-mitophagy axis is required for PTEN deletion-mediated endothelial cell survival under ox-LDL. Taken together, our results indicate that ox-LDL-induced endothelial cell damage is associated with PTEN overexpression, and inhibition of PTEN could promote endothelial survival via activating the AMPK-CREB-Mfn2-mitophagy signaling pathway. K E Y W O R D S AMPK-CREB-Mfn2 signaling pathway, endothelial cell dysfunction, Mfn2, mitophagy, ox-LDL, PTEN

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“…Acute ischaemic stroke causes extensive death of neurons which increases the resultant disability and mortality significantly . Accordingly, timely reperfusion therapy is important as an effective approach to reverse the damage to brain function and thus improve the prognosis in patients with ischaemia stroke . However, reperfusion itself brings about additional damage to ischaemic brain tissue, and this is termed as ‘ischaemia reperfusion injury’ which accounts for increased perioperative mortality .…”

Section: Introductionmentioning

confidence: 99%

Resveratrol attenuates cerebral ischaemia reperfusion injury via modulating mitochondrial dynamics homeostasis and activating AMPK‐Mfn1 pathway

Gao

Wang

et al. 2019

Int J Experimental Path

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Summary The pathogenesis of cerebral ischaemia reperfusion injury (IRI) has not been fully described. Accordingly, there is little effective drug available for the treatment of cerebral IRI. The aim of our study was to explore the exact role played by Mfn1‐mediated mitochondrial protection in cerebral IRI and evaluate the beneficial action of resveratrol on reperfused brain. Our study demonstrated that hypoxia‐reoxygenation (HR) injury caused N2a cell apoptosis and this process was highly affected by mitochondrial dysfunction. Decreased mitochondrial membrane potential, increased mitochondrial oxidative stress, and an activated mitochondrial apoptosis pathway were noted in HR‐treated N2a cells. Interestingly, resveratrol treatment could attenuate N2a cell apoptosis via sustaining mitochondrial homeostasis. Further, we found that resveratrol modulated mitochondrial performance via activating the Mfn1‐related mitochondrial protective system. Knockdown of Mfn1 could abolish the beneficial effects of resveratrol on HR‐treated N2a cells. Besides, we also report that resveratrol regulated Mfn1 expression via the AMPK pathway; inhibition of AMPK pathway also neutralized the anti‐apoptotic effect of resveratrol on N2a cells in the setting of cerebral IRI. Taken together our results show that mitochondrial damage is closely associated with the progression of cerebral IRI. In addition we also demonstrate the protective action played by resveratrol on reperfused brain and show that this effect is achieved via activating the AMPK‐Mfn1 pathway.

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Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

Cited by 322 publications

References 465 publications

MKP1 reduces neuroinflammation via inhibiting endoplasmic reticulum stress and mitochondrial dysfunction

MKP1 reduces neuroinflammation via inhibiting endoplasmic reticulum stress and mitochondrial dysfunction

PTEN inhibition attenuates endothelial cell apoptosis in coronary heart disease via modulating the AMPK–CREB–Mfn2‐mitophagy signaling pathway

Resveratrol attenuates cerebral ischaemia reperfusion injury via modulating mitochondrial dynamics homeostasis and activating AMPK‐Mfn1 pathway

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