Evidence map›Paper›PMID 42243457›Full record

ArticleCommunications biology2026

Cardiac-derived extracellular vesicles carrying miR-4433b-3p accelerate cognitive decline and brain aging by suppressing TP53INP2-mediated neuronal autophagy in mice.

Qian Cheng, Zhikang Cui, Shuyi Yu, Guixia Li, Hang Chen, Qian Yu, Jialin Han, Shuang Wu, Yan Jin, Yunshan Wang and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Qian Cheng *Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Zhikang Cui *Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Shuyi YuDepartment of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Guixia LiThe Laboratory Department of Heze Municipal Hospital, Heze, Shandong, China.
Hang ChenDepartment of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Qian YuDepartment of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Jialin HanDepartment of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Shuang WuDepartment of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Yan JinDepartment of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Yunshan WangDepartment of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.ORCID 0000-0001-5234-8752
Ming LiDepartment of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China. drmingli@yeah.net.ORCID 0009-0002-9307-7009
Zhiming LuDepartment of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China. luzhiming@sdu.edu.cn.ORCID 0000-0003-1228-5739

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82272414, 82572653
6 · The paper itself

Abstract

Brain aging is not an independent process, yet how systemic aging drives neural decline remains unclear. Here, we identified a circulating miR-4433b-3p, packaged within extracellular vesicles (EVs), as a trans-organ effector bridging cardiac aging with central nervous system (CNS) decline. Small RNA sequencing and human cohort validation revealed selective enrichment of miR-4433b-3p in aged plasma EVs (Op-EVs), correlating with blood biomarkers of brain aging. Source tracing in mice identified the aged heart as the major origin of miR-4433b-3p-laden EVs. Functionally, aged cardiac EVs (Oc-EVs) accumulated in the hippocampus, impaired memory and induced neuronal senescence. Mechanistically, miR-4433b-3p suppressed TP53INP2, a facilitator of autophagic flux, leading to disrupted autophagosome maturation. Restoring TP53INP2 or inhibiting miR-4433b-3p rescued neuronal autophagy and improved cognition. Collectively, these findings uncover a heart-brain axis by EV-mediated miRNA signaling, positioning cardiac EV-miR-4433b-3p as a circulating biomarker and potential therapeutic target for age-related cognitive decline.

Indexed as

AgingAutophagyBrainCognitive DysfunctionExtracellular VesiclesHeat-Shock ProteinsMicroRNAsMyocardiumNeuronsAnimalsHippocampusHumansMaleMiceMice, Inbred C57BLNuclear ProteinsHeat-Shock ProteinsMicroRNAsNuclear ProteinsTP53INP2 protein, humanTrp53bp2 protein, mouseTumor Suppressor Proteins

Identifiers

PMID42243457
PMCPMC13554194

What OpenQuestion holds

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Registered trials

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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.