See the published version of this article at Respiratory Research.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
The HDL from septic-ARDS patients with composition changes exacerbates pulmonary endothelial dysfunction and acute lung injury induced by cecal ligation and puncture (CLP) in mice
Yingmin Ma
Beijing Chaoyang Hospital
Corresponding Author
Jiawei Jin
Beijing Chaoyang Hospital, Capital Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5598-6039
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Respiratory Research.
Background: Septic-acute respiratory distress syndrome (ARDS), characterized by the acute lung injury (ALI) secondary to aberrant systemic inflammatory response, has high morbidity and mortality. Despite increased understanding of ALI pathogenesis, the therapies to prevent lung dysfunction underlying systemic inflammatory disorder remain elusive. The high density lipoprotein (HDL) has critical protective effects in sepsis and its dysfunction has a manifested contribution to septic organ failure. However, the adverse changes in HDL composition and function in septic-ARDS patients are large unknown.
Methods: To investigate HDL remodeling in septic-ARDS, we analyzed the changes of HDL composition from 40 patients with septic-ARDS (A-HDL) and 40 matched normal controls (N-HDL). To determine the deleterious functional remodeling of HDL, A-HDL or N-HDL was administrated to C57BL/6 and apoA-I knock-out (KO) mice after cecal ligation and puncture (CLP) procedure. Mouse lung microvascular endothelial cells (MLECs) were further treated by these HDLs to investigate whether the adverse effects of A-HDL were associated with endothelial dysfunction.
Results: Septic-ARDS patients showed significant changes of HDL composition, accompanied with significantly decreased HDL-C. We further indicated that A-HDL treatment aggravated CLP induced ALI. Intriguingly, these deleterious effects of A-HDL were associated with pulmonary endothelial dysfunction, rather than the increased plasma lipopolysaccharide (LPS). Further in vitro results demonstrated the direct effects of A-HDL on MLECs, including increased endothelial permeability, enhanced expressions of adhesion proteins and pro-inflammatory cytokines via activating NF-κB signaling and decreased junction protein expression.
Conclusions: Our results depicted the remodeling of HDL composition in sepsis, which predisposes lung to ARDS via inducing ECs dysfunction. These results also demonstrated the importance of circulating HDL in regulating alveolar homeostasis.
Keywords
ARDS, Sepsis, HDL dysfunction, pulmonary vascular endothelial cell, ALI
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 18 Sep, 2020
Published
On 04 Nov, 2020
No community comments so far
Editorial decision: Accept
On 19 Oct, 2020
Review #2 received
Received 18 Oct, 2020
Reviewer #2 agreed
On 07 Oct, 2020
Review #1 received
Received 07 Oct, 2020
Reviewers invited
Invitations sent on 02 Oct, 2020
Reviewer #1 agreed
On 02 Oct, 2020
Editor assigned
On 16 Sep, 2020
Submission checks complete
On 15 Sep, 2020
Editor invited
On 15 Sep, 2020
Version (no preprint)
Posted 15 May, 2020
Editorial decision: Major revision
On 20 Aug, 2020
Review #2 received
Received 19 Aug, 2020
Review #1 received
Received 17 Jul, 2020
Reviewer #2 agreed
On 16 Jul, 2020
Reviewers invited
Invitations sent on 15 Jul, 2020
Reviewer #1 agreed
On 15 Jul, 2020
Editor assigned
On 17 May, 2020
Submission checks complete
On 16 May, 2020
Editor invited
On 16 May, 2020
This version was not preprinted
No comments provided
Editor assigned
On 11 May, 2020
Submission checks complete
On 10 May, 2020
Editor invited
On 10 May, 2020
First submitted
On 09 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Pulmonology
Learn more about our company.
This preprint is under consideration at Respiratory Research. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
The HDL from septic-ARDS patients with composition changes exacerbates pulmonary endothelial dysfunction and acute lung injury induced by cecal ligation and puncture (CLP) in mice
Yingmin Ma
Beijing Chaoyang Hospital
Corresponding Author
Jiawei Jin
Beijing Chaoyang Hospital, Capital Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5598-6039
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 18 Sep, 2020
Published
On 04 Nov, 2020
No community comments so far
Editorial decision: Accept
On 19 Oct, 2020
Review #2 received
Received 18 Oct, 2020
Reviewer #2 agreed
On 07 Oct, 2020
Review #1 received
Received 07 Oct, 2020
Reviewers invited
Invitations sent on 02 Oct, 2020
Reviewer #1 agreed
On 02 Oct, 2020
Editor assigned
On 16 Sep, 2020
Submission checks complete
On 15 Sep, 2020
Editor invited
On 15 Sep, 2020
Version (no preprint)
Posted 15 May, 2020
Editorial decision: Major revision
On 20 Aug, 2020
Review #2 received
Received 19 Aug, 2020
Review #1 received
Received 17 Jul, 2020
Reviewer #2 agreed
On 16 Jul, 2020
Reviewers invited
Invitations sent on 15 Jul, 2020
Reviewer #1 agreed
On 15 Jul, 2020
Editor assigned
On 17 May, 2020
Submission checks complete
On 16 May, 2020
Editor invited
On 16 May, 2020
This version was not preprinted
No comments provided
Editor assigned
On 11 May, 2020
Submission checks complete
On 10 May, 2020
Editor invited
On 10 May, 2020
First submitted
On 09 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Pulmonology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Respiratory Research.
Background: Septic-acute respiratory distress syndrome (ARDS), characterized by the acute lung injury (ALI) secondary to aberrant systemic inflammatory response, has high morbidity and mortality. Despite increased understanding of ALI pathogenesis, the therapies to prevent lung dysfunction underlying systemic inflammatory disorder remain elusive. The high density lipoprotein (HDL) has critical protective effects in sepsis and its dysfunction has a manifested contribution to septic organ failure. However, the adverse changes in HDL composition and function in septic-ARDS patients are large unknown.
Methods: To investigate HDL remodeling in septic-ARDS, we analyzed the changes of HDL composition from 40 patients with septic-ARDS (A-HDL) and 40 matched normal controls (N-HDL). To determine the deleterious functional remodeling of HDL, A-HDL or N-HDL was administrated to C57BL/6 and apoA-I knock-out (KO) mice after cecal ligation and puncture (CLP) procedure. Mouse lung microvascular endothelial cells (MLECs) were further treated by these HDLs to investigate whether the adverse effects of A-HDL were associated with endothelial dysfunction.
Results: Septic-ARDS patients showed significant changes of HDL composition, accompanied with significantly decreased HDL-C. We further indicated that A-HDL treatment aggravated CLP induced ALI. Intriguingly, these deleterious effects of A-HDL were associated with pulmonary endothelial dysfunction, rather than the increased plasma lipopolysaccharide (LPS). Further in vitro results demonstrated the direct effects of A-HDL on MLECs, including increased endothelial permeability, enhanced expressions of adhesion proteins and pro-inflammatory cytokines via activating NF-κB signaling and decreased junction protein expression.
Conclusions: Our results depicted the remodeling of HDL composition in sepsis, which predisposes lung to ARDS via inducing ECs dysfunction. These results also demonstrated the importance of circulating HDL in regulating alveolar homeostasis.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5