Evidence map›Paper›PMID 29437833›Full record

ArticleCirculation research2018

Deficiency of Complement C3a and C5a Receptors Prevents Angiotensin II-Induced Hypertension via Regulatory T Cells.

Xiao-Hui Chen, Cheng-Chao Ruan, Qian Ge, Yu Ma, Jian-Zhong Xu, Ze-Bei Zhang, Jing-Rong Lin, Dong-Rui Chen, Ding-Liang Zhu, Ping-Jin Gao

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In one paragraph

Article in Circulation research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 1 pooled it
6.8field-weighted citation impact, top 2% 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.

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

59 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Pathophysiology and Clinical Relevance of Microvascular Remodeling in Arterial Hypertension.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2026
    Review
  4. Article
  5. Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026
    Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Overview of multifunctional Tregs in cardiovascular disease: From insights into cellular functions to clinical implications.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Review
  17. Article
  18. Immune and inflammatory mechanisms in hypertension.Nature reviews. Cardiology · 2024
    Review
  19. Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Xiao-Hui ChenFrom the State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension at Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, China (X.-H.C., C.-C.R., Q.G., Y.M., J.-Z.X., D.-R.C., D.-L.Z., P.-J.G.); and Laboratory of Vascular Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.) and Key Laboratory of Stem Cell Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.
Cheng-Chao RuanFrom the State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension at Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, China (X.-H.C., C.-C.R., Q.G., Y.M., J.-Z.X., D.-R.C., D.-L.Z., P.-J.G.); and Laboratory of Vascular Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.) and Key Laboratory of Stem Cell Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. gaopingjin@sibs.ac.cn ccruan@sibs.ac.cn.
Qian GeFrom the State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension at Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, China (X.-H.C., C.-C.R., Q.G., Y.M., J.-Z.X., D.-R.C., D.-L.Z., P.-J.G.); and Laboratory of Vascular Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.) and Key Laboratory of Stem Cell Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.
Yu MaFrom the State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension at Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, China (X.-H.C., C.-C.R., Q.G., Y.M., J.-Z.X., D.-R.C., D.-L.Z., P.-J.G.); and Laboratory of Vascular Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.) and Key Laboratory of Stem Cell Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.
Jian-Zhong XuFrom the State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension at Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, China (X.-H.C., C.-C.R., Q.G., Y.M., J.-Z.X., D.-R.C., D.-L.Z., P.-J.G.); and Laboratory of Vascular Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.) and Key Laboratory of Stem Cell Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.
Ze-Bei ZhangFrom the State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension at Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, China (X.-H.C., C.-C.R., Q.G., Y.M., J.-Z.X., D.-R.C., D.-L.Z., P.-J.G.); and Laboratory of Vascular Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.) and Key Laboratory of Stem Cell Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.
Jing-Rong LinFrom the State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension at Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, China (X.-H.C., C.-C.R., Q.G., Y.M., J.-Z.X., D.-R.C., D.-L.Z., P.-J.G.); and Laboratory of Vascular Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.) and Key Laboratory of Stem Cell Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.
Dong-Rui ChenFrom the State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension at Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, China (X.-H.C., C.-C.R., Q.G., Y.M., J.-Z.X., D.-R.C., D.-L.Z., P.-J.G.); and Laboratory of Vascular Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.) and Key Laboratory of Stem Cell Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.
Ding-Liang ZhuFrom the State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension at Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, China (X.-H.C., C.-C.R., Q.G., Y.M., J.-Z.X., D.-R.C., D.-L.Z., P.-J.G.); and Laboratory of Vascular Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.) and Key Laboratory of Stem Cell Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.
Ping-Jin GaoFrom the State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension at Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, China (X.-H.C., C.-C.R., Q.G., Y.M., J.-Z.X., D.-R.C., D.-L.Z., P.-J.G.); and Laboratory of Vascular Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.) and Key Laboratory of Stem Cell Biology (X.-H.C., C.-C.R., Z.-B.Z., J.-R.L., P.-J.G.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. gaopingjin@sibs.ac.cn ccruan@sibs.ac.cn.
Shanghai Institutes for Biological Sciences · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

rationaleInflammation and immunity play crucial roles in the development of hypertension. Complement activation-mediated innate immune response is involved in the regulation of hypertension and target-organ damage. However, whether complement-mediated T-cell functions could regulate blood pressure elevation in hypertension is still unclear.

objectiveWe aim to determine whether C3aR (complement component 3a receptor) and C5aR (complement component 5a receptor) could regulate blood pressure via modulating regulatory T cells (Tregs). METHODS AND

resultsWe showed that angiotensin II (Ang II)-induced hypertension resulted in an elevated expression of C3aR and C5aR in Foxp3 (forkhead box P3)+ Tregs. By using C3aR and C5aR DKO (double knockout) mice, we showed that C3aR and C5aR deficiency together strikingly decreased both systolic and diastolic blood pressure in response to Ang II compared with WT (wild type), single C3aR-deficient (C3aR-/-), or C5aR-deficient (C5aR-/-) mice. Flow cytometric analysis showed that Ang II-induced Treg reduction in the kidney and blood was also blocked in DKO mice. Histological analysis indicated that renal and vascular structure remodeling and damage after Ang II treatment were attenuated in DKO mice compared with WT mice. In vitro, Ang II was able to stimulate C3aR and C5aR expression in cultured CD4+CD25+ natural Tregs. CD3 and CD28 antibody stimuli downregulated Foxp3 expression in WT but not DKO Tregs. More important, depletion of Tregs with CD25 antibody abolished the protective effects against Ang II-induced hypertension and target-organ damage in DKO mice. Adoptive transfer of DKO Tregs showed much more profound protective effects against Ang II-induced hypertension than WT Treg transfer. Furthermore, we demonstrated that C5aR expression in Foxp3+ Tregs was higher in hypertensive patients compared with normotensive individuals.

conclusionsC3aR and C5aR DKO-mediated Treg function prevents Ang II-induced hypertension and target-organ damage. Targeting C3aR and C5aR in Tregs specifically may be an alternative novel approach for hypertension treatment.

Indexed as

Angiotensin IIAnimalsCells, CulturedHypertensionMaleMiceMice, Inbred BALB CReceptor, Anaphylatoxin C5aReceptors, Complement 3bT-Lymphocytes, RegulatoryAngiotensin IIReceptor, Anaphylatoxin C5aReceptors, Complement 3bhypertensionimmunologyinflammationregulatory T cellrenin–angiotensin system complement

Identifiers

PMID29437833
OpenAlexW2883093186

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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 OpenQuestion graph.