Evidence mapPaperPMID 41814130Full record

ArticleActa physiologica (Oxford, England)2026

Tacrolimus Induced Hypertension and Vascular Remodeling Includes Mechanisms of Cellular Senescence-The Protective Effect of Valsartan.

Lingyan Fei, Xiaohua Wang, Lingyi Kong, Tianjiao Cui, Pratik H Khedkar, Yunxiu Xiang, Dongliang Zhao, Junxuan Fang, Yulin Liang, Yangyang Zhang and 14 more

Abstract read
In one paragraph

Article in Acta physiologica (Oxford, England), 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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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

24 authors.

Lingyan FeiDepartment of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.ORCID https://orcid.org/0000-0002-9679-0101
Xiaohua WangDepartment of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
Lingyi KongDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Tianjiao CuiDepartment of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
Pratik H KhedkarInstitute of Translational Physiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.ORCID https://orcid.org/0000-0002-4778-7731
Yunxiu XiangDepartment of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
Dongliang ZhaoDepartment of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Junxuan FangDepartment of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
Yulin LiangDepartment of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
Yangyang ZhangDepartment of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
Nan XuDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Henan University, Kaifeng, China.
Xingyu QiuDepartment of Physiology, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, China.
Liang ZhaoDepartment of Physiology, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, China.
Gensheng ZhangDepartment of Nephrology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, and Key Laboratory of Diagnosis and Treatment of Neonatal Diseases of Zhejiang Province, Hangzhou, China.ORCID https://orcid.org/0000-0002-8157-6460
Yan LeiDepartment of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
Chun TangDepartment of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
Kongyang MaShenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, Centre for Infection and Immunity Studies (CIIS), School of Medicine, the Seventh Affiliated Hospital, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, Guangdong, China.ORCID https://orcid.org/0000-0002-9739-7686
Liwei LuDepartment of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong, China.ORCID https://orcid.org/0000-0002-8634-0967
Jin WeiSection of Nephrology, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, USA.
En Yin LaiDepartment of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.ORCID https://orcid.org/0000-0003-3074-6869
Pontus B PerssonInstitute of Translational Physiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.ORCID https://orcid.org/0000-0003-0926-2878
Andreas PatzakInstitute of Translational Physiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.
Zhihua ZhengDepartment of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
Shan JiangDepartment of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.

Funding

National Natural Science Foundation of China 3230090251National Natural Science Foundation of China 82100448National Natural Science Foundation of China 82170690National Natural Science Foundation of China 82500886Postdoctoral Science Foundation of China 2021M703715Research Start-up Fund of Post-doctoral of Sahsysu ZSQYRSFPD0032Science, Technology and Innovation Commission of Shenzhen Municipality JCYJ20180307150634856Science, Technology and Innovation Commission of Shenzhen Municipality JCYJ20210324123200003Shenzhen Medical Research Fund A2503011Shenzhen Science and Technology Innovation Program RCBS20231211090701008
6 · The paper itself

Abstract

aimCalcineurin inhibitors (CNI) such as tacrolimus (Tac) are the first-line treatment to prevent transplant rejection. However, CNI have adverse effects on blood vessels and renal function, which may be linked to cellular senescence. Valsartan, a common angiotensin II type 1 receptor (AT

methodsMicroperfusion and wire myography were employed to assess the contractile and dilatory functions of renal afferent arterioles (Af-Art) and mesenteric arteries, respectively. The expression of components of the renin-angiotensin system (RAS) and senescence-associated biomarkers was investigated using qPCR and immunohistochemistry.

resultsLong-term administration of Tac activated the RAS. Tac-induced microvascular remodeling in mesenteric arteries and Af-Art was mitigated by treatment with valsartan. Mice treated with Tac exhibited increased vasoconstriction in response to angiotensin II and reduced dilation to acetylcholine. Both effects were abolished by valsartan. Additionally, senescence-associated biomarkers were upregulated in mesenteric and renal resistance arteries from Tac-treated mice. Co-administration of Tac with valsartan or ABT-263, a senolytic agent, rescued Tac-induced microvascular injury and reduced hypertension (conscious mice, noninvasive tail-cuff system). Treatment with the antihypertensive drug amlodipine normalized blood pressure and downregulated senescence-associated beta-galactosidase in mesenteric arteries.

conclusionThese findings suggest that cellular senescence contributes to Tac-induced microvascular injury and hypertension and demonstrate the effectiveness of senolytic treatment for protection. Valsartan could reduce senescence indirectly by lowering blood pressure; a direct anti-senescence effect might also play a role in this context.

Indexed as

Cellular SenescenceHypertensionTacrolimusValsartanVascular RemodelingAngiotensin II Type 1 Receptor BlockersAnimalsAntihypertensive AgentsImmunosuppressive AgentsMaleMiceMice, Inbred C57BLRenin-Angiotensin SystemAngiotensin II Type 1 Receptor BlockersAntihypertensive AgentsImmunosuppressive AgentsTacrolimusValsartancellular senescencemicrovascular dysfunctionsenolytic drugtacrolimusvalsartan

Identifiers

PMID41814130
PMCPMC12979711

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.