Evidence mapPaperPMID 42218384Full record

ArticleCellular & molecular biology letters2026

KAP1 SUMOylates and stabilizes SR-A to facilitate glycated LDL transcytosis and accelerate atherosclerosis.

Meng Shu, Wenzhuo Cheng, Fangyang Yu, Liyin Zhang, Li Wang, Yan Shu, Ruonan Wang, Baorui Xue, Si Jin

Abstract read
In one paragraph

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

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Meng ShuDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Lake Road, East Lake Ecological Scenic, Wuhan, 430077, Hubei Province, China.
Wenzhuo ChengDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Lake Road, East Lake Ecological Scenic, Wuhan, 430077, Hubei Province, China.
Fangyang YuDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Lake Road, East Lake Ecological Scenic, Wuhan, 430077, Hubei Province, China.
Liyin ZhangDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Lake Road, East Lake Ecological Scenic, Wuhan, 430077, Hubei Province, China.
Li WangDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Lake Road, East Lake Ecological Scenic, Wuhan, 430077, Hubei Province, China.
Yan ShuDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Lake Road, East Lake Ecological Scenic, Wuhan, 430077, Hubei Province, China.
Ruonan WangDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Lake Road, East Lake Ecological Scenic, Wuhan, 430077, Hubei Province, China.
Baorui XueDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Lake Road, East Lake Ecological Scenic, Wuhan, 430077, Hubei Province, China.
Si JinDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Lake Road, East Lake Ecological Scenic, Wuhan, 430077, Hubei Province, China. Jinsi@hust.edu.cn.

Funding

National Natural Science Foundation of China 82070862
6 · The paper itself

Abstract

backgroundAtherosclerosis (AS)-associated cardiovascular disease is the main cause of global mortality. The excessive retention of glycated low-density lipoprotein (G-LDL) under the vascular endothelium promotes AS. In addition, G-LDL supports a role in promoting the expression of scavenger receptor A (SR-A), increasing SR-A-mediated transcytosis of G-LDL in endothelial cells (ECs), consequently accelerating the progression of atherosclerosis. However, the underlying mechanism used by G-LDL to promote SR-A expression has not been elucidated, thus representing the aim of this work.

methodsThe protein-protein interaction of the E3 SUMO ligase KRAB structural domain-associated protein 1 (KAP1) and SR-A were confirmed by co-immunoprecipitation (co-IP)-based immunoblotting and immunofluorescence in human umbilical vein endothelial cells (HUVECs). G-LDL uptake and transcytosis in KAP1-silencing or overexpressing HUVECs were assessed. The effect of KAP1 on de-ubiquitination and SUMOylation of SR-A was determined by co-IP-based immunoblotting. The role of KAP1 on G-LDL-induced atherosclerosis was tested by adenovirus-mediated knockdown in ApoE

resultsKAP1 was identified as an enhancer of SR-A, promoting its expression. KAP1 bound to SR-A and promoted SUMO1 modification of the SR-A lysine (K)22, which hampers K48-linked ubiquitination and proteasomal degradation of SR-A. KAP1 deficiency attenuated G-LDL-induced SR-A activation both in vitro and in vivo, reduced aortic G-LDL retention, and consequently, atherosclerotic vulnerable plaque formation in murine models.

conclusionsThis study identifies a SUMOylation-ubiquitination crosstalk that governs SR-A stability, revealing KAP1 as a key molecular switch controlling SR-A turnover in endothelial cells. These findings provide a mechanistic basis for how G-LDL accelerates atherosclerosis.

Indexed as

AtherosclerosisLipoproteins, LDLScavenger Receptors, Class ATranscytosisTripartite Motif-Containing Protein 28AnimalsApolipoproteins EGlycated ProteinsGlycation End Products, AdvancedHumansHuman Umbilical Vein Endothelial CellsMaleMiceMice, Inbred C57BLSumoylationUbiquitinationApolipoproteins Eglycated lipoproteins, LDLGlycated ProteinsGlycation End Products, AdvancedLipoproteins, LDLScavenger Receptors, Class ATRIM28 protein, humanTripartite Motif-Containing Protein 28AtherosclerosisGlycated LDLKAP1SR-ASUMOylationTranscytosis

Identifiers

PMID42218384
PMCPMC13435427

What Socratic holds

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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 Socratic graph.