Evidence map›Paper›PMID 35152717›Full record

ArticleCirculation research2022

Targeting CaMKII-δ9 Ameliorates Cardiac Ischemia/Reperfusion Injury by Inhibiting Myocardial Inflammation.

Yuan Yao, Fan Li, Mao Zhang, Li Jin, Peng Xie, Dairu Liu, Junxia Zhang, Xinli Hu, Fengxiang Lv, Haibao Shang and 7 more

Open access · bronzeAbstract read
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In one paragraph

Article in Circulation research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
7.8field-weighted citation impact, top 2% 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

51 citing papers in PubMed, 96 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 3 countries.

Yuan Yao *State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology (Y.Y., F. Li, M.Z., L.J., P.X., D.L., J.Z., X.H., F. Lv, H.S., W.Z., X.S., R.-P.X., Y.Z.), Peking University, Beijing, China.
Fan Li *State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology (Y.Y., F. Li, M.Z., L.J., P.X., D.L., J.Z., X.H., F. Lv, H.S., W.Z., X.S., R.-P.X., Y.Z.), Peking University, Beijing, China.
Mao Zhang *State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology (Y.Y., F. Li, M.Z., L.J., P.X., D.L., J.Z., X.H., F. Lv, H.S., W.Z., X.S., R.-P.X., Y.Z.), Peking University, Beijing, China.ORCID 0000-0002-5283-6497
Li JinState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology (Y.Y., F. Li, M.Z., L.J., P.X., D.L., J.Z., X.H., F. Lv, H.S., W.Z., X.S., R.-P.X., Y.Z.), Peking University, Beijing, China.
Peng XieState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology (Y.Y., F. Li, M.Z., L.J., P.X., D.L., J.Z., X.H., F. Lv, H.S., W.Z., X.S., R.-P.X., Y.Z.), Peking University, Beijing, China.
Dairu LiuState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology (Y.Y., F. Li, M.Z., L.J., P.X., D.L., J.Z., X.H., F. Lv, H.S., W.Z., X.S., R.-P.X., Y.Z.), Peking University, Beijing, China.
Junxia ZhangState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology (Y.Y., F. Li, M.Z., L.J., P.X., D.L., J.Z., X.H., F. Lv, H.S., W.Z., X.S., R.-P.X., Y.Z.), Peking University, Beijing, China.
Xinli HuState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology (Y.Y., F. Li, M.Z., L.J., P.X., D.L., J.Z., X.H., F. Lv, H.S., W.Z., X.S., R.-P.X., Y.Z.), Peking University, Beijing, China.ORCID 0000-0003-4911-5354
Fengxiang LvState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology (Y.Y., F. Li, M.Z., L.J., P.X., D.L., J.Z., X.H., F. Lv, H.S., W.Z., X.S., R.-P.X., Y.Z.), Peking University, Beijing, China.
Haibao ShangState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology (Y.Y., F. Li, M.Z., L.J., P.X., D.L., J.Z., X.H., F. Lv, H.S., W.Z., X.S., R.-P.X., Y.Z.), Peking University, Beijing, China.
Wen ZhengState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology (Y.Y., F. Li, M.Z., L.J., P.X., D.L., J.Z., X.H., F. Lv, H.S., W.Z., X.S., R.-P.X., Y.Z.), Peking University, Beijing, China.
Xueting SunState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology (Y.Y., F. Li, M.Z., L.J., P.X., D.L., J.Z., X.H., F. Lv, H.S., W.Z., X.S., R.-P.X., Y.Z.), Peking University, Beijing, China.
Jiaxin DuanmuInstitute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, School of Basic Medical Sciences, Ministry of Education, Peking University Health Science Center, Beijing, China (J.D., Y.Z.).
Fujian WuState Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (F.W., F. Lan).
Feng LanState Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (F.W., F. Lan).ORCID 0000-0002-9038-4014
Rui-Ping XiaoState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology (Y.Y., F. Li, M.Z., L.J., P.X., D.L., J.Z., X.H., F. Lv, H.S., W.Z., X.S., R.-P.X., Y.Z.), Peking University, Beijing, China.
Yan ZhangState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology (Y.Y., F. Li, M.Z., L.J., P.X., D.L., J.Z., X.H., F. Lv, H.S., W.Z., X.S., R.-P.X., Y.Z.), Peking University, Beijing, China.ORCID 0000-0002-8322-467X
Xerox (France) · FRChinese Academy of Medical Sciences & Peking Union Medical College · CNMinistry of Education · ROPeking University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCaMKII (Ca

methodsThe role and mechanism of CaMKII-δ9 in cardiac I/R injury were investigated in mice in vivo, neonatal rat ventricular myocytes, and human embryonic stem cell-derived cardiomyocytes.

resultsWe demonstrate that CaMKII-δ9 inhibition with knockdown or knockout of its feature exon, exon 16, protects the heart against I/R-elicited injury and subsequent heart failure. I/R-induced cardiac inflammation was also ameliorated by CaMKII-δ9 inhibition, and compared with the previously well-studied CaMKII-δ2, CaMKII-δ9 overexpression caused more profound cardiac inflammation. Mechanistically, in addition to IKKβ (inhibitor of NF-κB [nuclear factor-κB] kinase subunit β), CaMKII-δ9, but not δ2, directly interacted with IκBα (NF-κB inhibitor α) with its feature exon 13-16-17 combination and increased IκBα phosphorylation and consequently elicited more pronounced activation of NF-κB signaling and inflammatory response. Furthermore, the essential role of CaMKII-δ9 in myocardial inflammation and damage was confirmed in human cardiomyocytes.

conclusionsWe not only identified CaMKII-δ9-IKK/IκB-NF-κB signaling as a new regulator of human cardiomyocyte inflammation but also demonstrated that specifically targeting CaMKII-δ9, the most abundant CaMKII-δ splice variant in human heart, markedly suppresses I/R-induced cardiac NF-κB activation, inflammation, and injury and subsequently ameliorates myocardial remodeling and heart failure, providing a novel therapeutic strategy for various ischemic heart diseases.

Indexed as

Heart FailureMyocardial Reperfusion InjuryMyocarditisAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2InflammationIschemiaMiceMyocytes, CardiacNF-kappa BNF-KappaB Inhibitor alphaRatsCalcium-Calmodulin-Dependent Protein Kinase Type 2NF-kappa BNF-KappaB Inhibitor alphaanimalshumansmicemuscle cellsrats

Identifiers

PMID35152717
OpenAlexW4213040841

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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.