Evidence map›Paper›PMID 35354793›Full record

ArticleCell death & disease2022

Irisin protects against vascular calcification by activating autophagy and inhibiting NLRP3-mediated vascular smooth muscle cell pyroptosis in chronic kidney disease.

Qi Pang, Peiwen Wang, Yajing Pan, Xingtong Dong, Ting Zhou, Xinyu Song, Aihua Zhang

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07654231 (Reducing Inflammation to Improve Vascular and Bone Outcomes With Low-dose Colchicine in CKD), which is not on this map. Cited by 86 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 1 pooled it
12.0field-weighted citation impact, top 1% of its field
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.

NCT07654231 phase2not yet recruitingnot on this mapstarted 2026, after this paper: background citation

Reducing Inflammation to Improve Vascular and Bone Outcomes With Low-dose Colchicine in CKD: A Pilot Randomized Open-Label Trial (RESOLVE-CKD Trial)

TypeinterventionalSponsorUniversity of Texas Southwestern Medical CenterRan2026 to 2027Enrolled60ConditionsChronic Kidney Disease Mineral and Bone Disorder, Hypertension, Diabetes, DyslipidemiaArmsLow-dose Colchicine at 0.5mg daily, Usual Care
3 · Its place in the literature

Who cites it

86 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.

  1. Protective role of irisin on bone in osteoporosis: a systematic review of rodent studies.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025
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  15. Irisin protects against atherosclerosis in ApoEMolecular and cellular biochemistry · 2026
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26 more citing papers are in PubMed but not listed here.

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

7 authors at 1 institution in 1 country.

Qi PangDepartment of Nephrology, Xuanwu Hospital, Capital Medical University, Changchun Street 45#, 100053, Beijing, China.ORCID 0000-0002-2969-3336
Peiwen WangDepartment of Nephrology, Xuanwu Hospital, Capital Medical University, Changchun Street 45#, 100053, Beijing, China.ORCID 0000-0002-2744-183X
Yajing PanDepartment of Nephrology, Xuanwu Hospital, Capital Medical University, Changchun Street 45#, 100053, Beijing, China.ORCID 0000-0001-9259-9521
Xingtong DongDepartment of Nephrology, Xuanwu Hospital, Capital Medical University, Changchun Street 45#, 100053, Beijing, China.ORCID 0000-0003-4456-4011
Ting ZhouDepartment of Nephrology, Xuanwu Hospital, Capital Medical University, Changchun Street 45#, 100053, Beijing, China.ORCID 0000-0002-1872-8046
Xinyu SongDepartment of Nephrology, Xuanwu Hospital, Capital Medical University, Changchun Street 45#, 100053, Beijing, China.ORCID 0000-0002-6106-0774
Aihua ZhangDepartment of Nephrology, Xuanwu Hospital, Capital Medical University, Changchun Street 45#, 100053, Beijing, China. rosezhang998@sina.com.ORCID 0000-0003-2949-4633
Capital Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Irisin protects the cardiovascular system against vascular diseases. However, its role in chronic kidney disease (CKD) -associated vascular calcification (VC) and the underlying mechanisms remain unclear. In the present study, we investigated the potential link among Irisin, pyroptosis, and VC under CKD conditions. During mouse vascular smooth muscle cell (VSMC) calcification induced by β-glycerophosphate (β-GP), the pyroptosis level was increased, as evidenced by the upregulated expression of pyroptosis-related proteins (cleaved CASP1, GSDMD-N, and IL1B) and pyroptotic cell death (increased numbers of PI-positive cells and LDH release). Reducing the pyroptosis levels by a CASP1 inhibitor remarkably decreased calcium deposition in β-GP-treated VSMCs. Further experiments revealed that the pyroptosis pathway was activated by excessive reactive oxygen species (ROS) production and subsequent NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in calcified VSMCs. Importantly, Irisin effectively inhibited β-GP-induced calcium deposition in VSMCs in vitro and in mice aortic rings ex vivo. Overexpression of Nlrp3 attenuated the suppressive effect of Irisin on VSMC calcification. In addition, Irisin could induce autophagy and restore autophagic flux in calcified VSMCs. Adding the autophagy inhibitor 3-methyladenine or chloroquine attenuated the inhibitory effect of Irisin on β-GP-induced ROS production, NLRP3 inflammasome activation, pyroptosis, and calcification in VSMCs. Finally, our in vivo study showed that Irisin treatment promoted autophagy, downregulated ROS level and thereby suppressed pyroptosis and medial calcification in aortic tissues of adenine-induced CKD mice. Together, our findings for the first time demonstrated that Irisin protected against VC via inducing autophagy and inhibiting VSMC pyroptosis in CKD, and Irisin might serve as an effective therapeutic agent for CKD-associated VC.

Indexed as

Renal Insufficiency, ChronicVascular CalcificationAnimalsAutophagyCalciumCaspase 1InflammasomesMiceMuscle, Smooth, VascularNLR Family, Pyrin Domain-Containing 3 ProteinPyroptosisReactive Oxygen SpeciesCalciumCaspase 1InflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseReactive Oxygen Species

Identifiers

PMID35354793
PMCPMC8967887
OpenAlexW4220653278

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Registered trials

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.