Evidence map›Paper›PMID 35930089›Full record

ArticleInflammation2023

PCSK9 Promotes Endothelial Dysfunction During Sepsis Via the TLR4/MyD88/NF-κB and NLRP3 Pathways.

Longxiang Huang, Yuanjing Li, Zhe Cheng, Zi Lv, Suxin Luo, Yong Xia

Abstract read
PubMed Publisher
In one paragraph

Article in Inflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 2 pooled it
17.2field-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.

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

64 citing papers in PubMed, 2 syntheses or guidelines pooled it, 92 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection.Journal of the American College of Cardiology · 2023
    Trial
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. Article

4 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

6 authors at 3 institutions in 2 countries.

Longxiang HuangDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.ORCID http://orcid.org/0000-0002-7606-1235
Yuanjing LiDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Zhe ChengDepartment of Cardiology, Chongqing University, Three Gorges Hospital & Chongqing Three Gorges Central Hospital, Chongqing, 404000, China.
Zi LvDepartment of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Suxin LuoDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. luosuxin@hospital.cqmu.edu.cn.
Yong XiaDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. yong.xia@osumc.edu.
The Affiliated Yongchuan Hospital of Chongqing Medical University · CNChongqing University · CNGuangzhou Medical University · CN

Funding

National Natural Science Foundation of China 82070238
6 · The paper itself

Abstract

Endothelial dysfunction often accompanies sepsis. We aimed to explore the role of PCSK9 in septic endothelial dysfunction. Sepsis was induced by lipopolysaccharide (LPS) treatment of human umbilical vein endothelial cells (HUVECs) in vitro and cecal ligation and puncture (CLP) surgery in mice in vivo. Evolocumab (EVC) and Pep 2-8, PCSK9 inhibitors, were subsequently used to determine the role of PCSK9 in sepsis-induced endothelial dysfunction in vitro and in vivo, respectively. In addition, the TLR4 agonist, Kdo2-Lipid A ammonium (KLA), was used to determine the related mechanism. Protein expression of eNOS, VE-cadherin, PCSK9, TLR4, MyD88, p-p65, p65, NLRP3, ASC, and caspase-1 p20 in mice aortas and HUVECs was measured by western blotting, while mRNA expression of TNFα, IL-1β, and IL-18 was determined by qRT-PCR. The level of inflammatory cytokines of mouse aortas was visualized by immunohistochemistry. Vasodilation of the aorta was detected by vascular reactivity experiments. The 96-h survival rate after CLP was assessed. Our findings showed that the expression of eNOS and VE-cadherin decreased, and PCSK9 expression increased, in septic HUVECs or mice. Inhibition of PCSK9 increased eNOS and VE-cadherin expression. Activation of the TLR4/MyD88/NF-κB and NLRP3 pathways may be responsible for PCSK9-induced endothelial dysfunction in sepsis. Vascular reactivity tests and survival studies showed that inhibition of PCSK9 could prevent the decrease in endothelium-dependent vasodilation function and improve the survival rates of septic mice. In summary, our results suggested that increased PCSK9 expression during sepsis activated the TLR4/MyD88/NF-κB and NLRP3 pathways to induce inflammation, which resulted in vascular endothelial dysfunction and decreased survival rates. Thus, inhibition of PCSK9 may be a potential clinical therapeutic target to improve vascular endothelial function in sepsis.

Indexed as

NF-kappa BSepsisAnimalsHumansHuman Umbilical Vein Endothelial CellsMiceMyeloid Differentiation Factor 88NLR Family, Pyrin Domain-Containing 3 ProteinProprotein Convertase 9Toll-Like Receptor 4Myd88 protein, mouseMyeloid Differentiation Factor 88NF-kappa BNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mousePCSK9 protein, humanPcsk9 protein, mouseProprotein Convertase 9TLR4 protein, humanTlr4 protein, mouseToll-Like Receptor 4Endothelial dysfunctionInflammationPCSK9Sepsis

Identifiers

PMID35930089
OpenAlexW4289861020

What Socratic holds

Textmetadata
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.