Evidence map›Paper›PMID 29669712›Full record

ArticleCirculation research2018

Endoplasmic Reticulum Chaperone GRP78 Protects Heart From Ischemia/Reperfusion Injury Through Akt Activation.

Xukun Bi, Guangyu Zhang, Xiaoding Wang, Chau Nguyen, Herman I May, Xiaoting Li, Ali A Al-Hashimi, Richard C Austin, Thomas G Gillette, Guosheng Fu and 2 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed
8.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

98 citing papers in PubMed, 149 citations in OpenAlex.

  1. Review
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  10. Spatial protein redistribution: wandering but not lost.Cellular and molecular life sciences : CMLS · 2025
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38 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Xukun BiFrom the Department of Cardiology, Biomedical Research (Therapy) Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China (X.B., X.L., G.F.).
Guangyu ZhangDivision of Cardiology, Department of Internal Medicine (X.B., G.Z., X.W., C.N., H.I.M., T.G.G., Z.V.W., J.A.H.).
Xiaoding WangDivision of Cardiology, Department of Internal Medicine (X.B., G.Z., X.W., C.N., H.I.M., T.G.G., Z.V.W., J.A.H.).
Chau NguyenDivision of Cardiology, Department of Internal Medicine (X.B., G.Z., X.W., C.N., H.I.M., T.G.G., Z.V.W., J.A.H.).
Herman I MayDivision of Cardiology, Department of Internal Medicine (X.B., G.Z., X.W., C.N., H.I.M., T.G.G., Z.V.W., J.A.H.).
Xiaoting LiFrom the Department of Cardiology, Biomedical Research (Therapy) Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China (X.B., X.L., G.F.).
Ali A Al-HashimiDepartment of Medicine, Hamilton Center for Kidney Research, McMaster University and the Research Institute of St. Joseph's Healthcare Hamilton, ON, Canada (A.A.A.-H., R.C.A.).
Richard C AustinDepartment of Medicine, Hamilton Center for Kidney Research, McMaster University and the Research Institute of St. Joseph's Healthcare Hamilton, ON, Canada (A.A.A.-H., R.C.A.).
Thomas G GilletteDivision of Cardiology, Department of Internal Medicine (X.B., G.Z., X.W., C.N., H.I.M., T.G.G., Z.V.W., J.A.H.).
Guosheng FuFrom the Department of Cardiology, Biomedical Research (Therapy) Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China (X.B., X.L., G.F.).
Zhao V WangDivision of Cardiology, Department of Internal Medicine (X.B., G.Z., X.W., C.N., H.I.M., T.G.G., Z.V.W., J.A.H.) zhao.wang@utsouthwestern.edu joseph.hill@utsouthwestern.edu.
Joseph A HillDivision of Cardiology, Department of Internal Medicine (X.B., G.Z., X.W., C.N., H.I.M., T.G.G., Z.V.W., J.A.H.).
Sir Run Run Shaw Hospital · CNRenmin Hospital of Wuhan University · CNSouthwestern Medical Center · USZhejiang University · CN

Funding

Role of the Xbp1s/GFAT1 axis in pathological cardiac remodellingR01HL137723 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI WANG, ZHAO · 2017 to 2025
$4.3M
Mechanisms of obesity-dependent alterations in cardiomyocyte metabolismR01HL128215 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI HILL, JOSEPH A · 2017 to 2020
$1.6M
FoxO-dependent Control of Cardiovascular RemodelingR01HL126012 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI HILL, JOSEPH A · 2016 to 2019
$1.6M
STIM1: Master Regulator of Calcium Homeostasis in CardiomyocytesR01HL120732 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI HILL, JOSEPH A · 2013 to 2016
$1.6M
CIHR MOP‐286787NHLBI NIH HHS R01 HL120732NHLBI NIH HHS R01 HL126012NHLBI NIH HHS R01 HL128215NHLBI NIH HHS R01 HL137723
6 · The paper itself

Abstract

rationaleRestoration of coronary artery blood flow is the most effective means of ameliorating myocardial damage triggered by ischemic heart disease. However, coronary reperfusion elicits an increment of additional injury to the myocardium. Accumulating evidence indicates that the unfolded protein response (UPR) in cardiomyocytes is activated by ischemia/reperfusion (I/R) injury. Xbp1s (spliced X-box binding protein 1), the most highly conserved branch of the unfolded protein response, is protective in response to cardiac I/R injury. GRP78 (78 kDa glucose-regulated protein), a master regulator of the UPR and an Xbp1s target, is upregulated after I/R. However, its role in the protective response of Xbp1s during I/R remains largely undefined.

objectiveTo elucidate the role of GRP78 in the cardiomyocyte response to I/R using both in vitro and in vivo approaches. METHODS AND

resultsSimulated I/R injury to cultured neonatal rat ventricular myocytes induced apoptotic cell death and strong activation of the UPR and GRP78. Overexpression of GRP78 in neonatal rat ventricular myocytes significantly protected myocytes from I/R-induced cell death. Furthermore, cardiomyocyte-specific overexpression of GRP78 ameliorated I/R damage to the heart in vivo. Exploration of underlying mechanisms revealed that GRP78 mitigates cellular damage by suppressing the accumulation of reactive oxygen species. We go on to show that the GRP78-mediated cytoprotective response involves plasma membrane translocation of GRP78 and interaction with PI3 kinase, culminating in stimulation of Akt. This response is required as inhibition of the Akt pathway significantly blunted the antioxidant activity and cardioprotective effects of GRP78.

conclusionsI/R induction of GRP78 in cardiomyocytes stimulates Akt signaling and protects against oxidative stress, which together protect cells from I/R damage.

Indexed as

Unfolded Protein ResponseAnimalsApoptosisCells, CulturedEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsMiceMice, Inbred C57BLMice, TransgenicMyocardial IschemiaMyocardial Reperfusion InjuryMyocytes, CardiacOxidative StressPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRatsEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsHspa5 protein, mousePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReactive Oxygen Speciescell deathmyocardiumreactive oxygen speciesreperfusion injuryunfolded protein response

Identifiers

PMID29669712
PMCPMC5970094
OpenAlexW2885985546

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.