Evidence map›Paper›PMID 41067595›Full record

ArticlePharmacological research2025

Endothelial adenosine receptor 2A loss alleviates diabetic vascular calcification by blocking CREB1-SNAI1-driven EndMT.

Yaqi Zhou, Dingwei Zhao, Qian Ma, Jiean Xu, Yongfeng Cai, Qiuhua Yang, Qingen Da, Kian Sheridan, Chunxiang Zhang, Clint L Miller and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pharmacological research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

14 authors.

Yaqi ZhouState Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China; Department of Physiology, Research Center of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, 232 Waihuan East Road, University Town, Guangzhou 510006, China; Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Dingwei ZhaoState Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China; Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA; Departments of Ophthalmology, Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Qian MaVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA; Departments of Ophthalmology, Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Jiean XuDepartment of Physiology, Research Center of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, 232 Waihuan East Road, University Town, Guangzhou 510006, China; Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Yongfeng CaiVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA; Departments of Ophthalmology, Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Qiuhua YangDepartment of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA.
Qingen DaState Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
Kian SheridanEmory University, Atlanta, GA 30322, USA.
Chunxiang ZhangDepartment of Cardiology, Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000, China.
Clint L MillerDepartment of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
Rajeev MalhotraCardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Suowen XuDepartment of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China; Anhui Provincial Key Laboratory of Metabolic Health and Panvascular Diseases, Hefei, 230001, China; Institute of Endocrine and Metabolic Diseases, University of Science and Technology of China, Hefei 230001, China.
Mei HongState Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China. Electronic address: meihong.sz@pku.edu.cn.
Yuqing HuoVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA; Departments of Ophthalmology, Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: yuqing.huo@bcm.edu.

Funding

Multimodal genetic regulatory architecture of coronary artery diseaseR01HL148239 · NHLBI · UNIVERSITY OF VIRGINIA · PI Clint L Miller · 2019 to 2026
$4.2M
Myeloid glycolysis in pathological ocular angiogenesisR01EY030500 · NEI · AUGUSTA UNIVERSITY · PI CALDWELL, RUTH B, HUO, YUQING · 2019 to 2023
$2.6M
Functional genomics investigation of pleiotropic vascular disease lociR01HL164577 · NHLBI · UNIVERSITY OF VIRGINIA · PI MILLER, CLINT L · 2022 to 2025
$2.3M
Adenosine receptor 2A in subretinal fibrosisR01EY033737 · NEI · BAYLOR COLLEGE OF MEDICINE · PI Ruth B Caldwell, YUQING HUO · 2022 to 2026
$2.1M
"Myeloid PFKFB3 in subretinal fibrosis"R01EY033369 · NEI · AUGUSTA UNIVERSITY · PI CALDWELL, RUTH B, HUO, YUQING · 2022 to 2025
$1.6M
NEI NIH HHS R01 EY030500NEI NIH HHS R01 EY033369NEI NIH HHS R01 EY033737NHLBI NIH HHS R01 HL148239NHLBI NIH HHS R01 HL164577
6 · The paper itself

Abstract

Vascular calcification (VC), a common complication associated with diabetes mellitus (DM), substantially increases the risk of cardiovascular diseases and is associated with elevated mortality in individuals with DM. Endothelial-to-mesenchymal transition (EndMT) imparts phenotypic plasticity to vascular endothelial cells (VECs), granting them the potential for osteogenic differentiation, which is a crucial mechanism in regulating VC. Notably, adenosine-ADORA2A-mediated endothelial dysfunction plays a pivotal regulatory role in cardiovascular diseases. However, the specific role of endothelial ADORA2A in diabetic VC remains to be elucidated. In this study, we found that ADORA2A was upregulated in the endothelium of diabetic mice and cultured human aortic endothelial cells (HAECs) with high glucose treatment. Deletion of endothelial Adora2a or pharmacologic inhibition of ADORA2A with KW6002 attenuated EndMT, osteogenic differentiation, and calcium deposit in diabetic aortas of Ins2

Indexed as

Cyclic AMP Response Element-Binding ProteinDiabetes Mellitus, ExperimentalDiabetic AngiopathiesEndothelial CellsEpithelial-Mesenchymal TransitionReceptor, Adenosine A2ASnail Family Transcription FactorsVascular CalcificationAnimalsCells, CulturedEndothelial-Mesenchymal TransitionHumansMaleMiceMice, Inbred C57BLMice, KnockoutADORA2A protein, humanAdora2a protein, mouseCREB1 protein, humanCreb1 protein, mouseCyclic AMP Response Element-Binding ProteinReceptor, Adenosine A2ASNAI1 protein, humanSnail Family Transcription FactorsAdenosine receptor 2 ACREB1Diabetes mellitusEndothelial-to-mesenchymal transitionSNAI1Vascular calcification

Identifiers

PMID41067595
PMCPMC13331242

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.