Evidence mapPaperPMID 38803180Full record

ArticleCombinatorial chemistry & high throughput screening2025

SGLT2i Alleviates Atherosclerosis by Inhibiting NHE1 Activation to Protect against Macrophage Senescence Induced by Angiotensin II.

Yang Cao, Xiangang Mo, Tianhui Wang, Qian Tian, Shuping Zhang, Yuan Zhu, Lan Wang, Nannan Li, Miao Lei

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Article in Combinatorial chemistry & high throughput screening, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 citing paper in PubMed.

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5 · Who and what money

Authors and funding

9 authors.

Yang CaoDepartment of geriatrics, Guizhou Medical University, 9 Beijing Road, Yunyan District, Guiyang City, 550000, China.
Xiangang MoDepartment of geriatrics, Guizhou Medical University, 9 Beijing Road, Yunyan District, Guiyang City, 550000, China.
Tianhui WangDepartment of geriatrics, Guizhou Medical University, 9 Beijing Road, Yunyan District, Guiyang City, 550000, China.
Qian TianDepartment of geriatrics, Guizhou Medical University, 9 Beijing Road, Yunyan District, Guiyang City, 550000, China.
Shuping ZhangDepartment of Geriatrics, Jingyang Hospital Affiliated to Guizhou Medical University, 547 Jinyang South Road, Guiyang City, 550000, China.
Yuan ZhuDepartment of geriatrics, Guizhou Medical University, 9 Beijing Road, Yunyan District, Guiyang City, 550000, China.
Lan WangDepartment of Geriatrics, Affiliated Hospital of Guizhou Medical University, 28 Guiyi Street, Yunyan District, 550000, China.
Nannan LiDepartment of geriatrics, Guizhou Medical University, 9 Beijing Road, Yunyan District, Guiyang City, 550000, China.
Miao LeiOrthopedics Department, The First Affiliated Hospital of Chongqing Medical University, Medical College Road, Yuzhong District, Chongqing, 400000, China.

Funding

National Science Foundation of China 82160097
6 · The paper itself

Abstract

backgroundSodium-dependent glucose transporter (SGLT2) inhibitors (SGLT2i) have been found to have anti-atherosclerotic effects in clinical treatment.

objectivesThe aim of this study was to explore whether angiotensin II (Ang II) induces changes in the expression of Na+/H+ exchanger of cytoplasmic membrane channel proteins (NHE1) and SGLT2 in macrophages and whether dapagliflozin (DAPA), an SGLT2i, protects against Ang II induced macrophage senescence by inhibiting NHE1 activation to alleviate Atherosclerosis (AS).

methodsAfter intervention with DAPA plus gavage or feeding them a high-fat diet, the mice's aortas were dissected, and oil red O staining was performed. Cell proliferation and toxicity detection, western blot, immunofluorescence, and β-galactosidase staining methods were adopted to detect cell activity, expressions of senescence-related genes, and number of senescent cells after different concentrations of Ang II or DAPA or plasmid NHE1 were treated with RAW264.7 cells.

results(1) The formation of AS plaques in ApoE -/- mice showed a downward trend under DAPA. (2) After the intervention of Ang II, the cell activity of RAW264.7 decreased, and the expression of senescent cells and related genes increased. (3) Under the Ang II condition, the expression of SGLT2 and NHE1 increased, and SGLT2, NHE1, and senescence-related genes decreased with the addition of DAPA. (4) The expression of NHE1, senescent cells and related genes decreased in RAW264.7 cells after DAPA treatment with plasmid NHE1 intervention.

conclusionSGLT2i alleviates atherosclerosis by inhibiting NHE1 activation to protect against macrophage senescence induced by Ang II.

Indexed as

Angiotensin IIAtherosclerosisBenzhydryl CompoundsCellular SenescenceGlucosidesMacrophagesSodium-Glucose Transporter 2 InhibitorsSodium-Hydrogen Exchanger 1AnimalsMaleMiceMice, Inbred C57BLRAW 264.7 CellsSodium-Glucose Transporter 2Angiotensin IIBenzhydryl CompoundsdapagliflozinGlucosidesSlc9a1 protein, mouseSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsSodium-Hydrogen Exchanger 1ASatherosclerosismacrophage.NHE1senescenceSGLT2i

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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.