Pharmacological inhibition of the ACE/Ang-2/AT1 axis alleviates mechanical ventilation-induced pulmonary fibrosis
Copyright © 2024. Published by Elsevier B.V..
Mechanical ventilation (MV) is an essential therapy for acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. However, it can also induce mechanical ventilation-induced pulmonary fibrosis (MVPF) and the underlying mechanism remains unknown. Based on a mouse model of MVPF, the present study aimed to explore the role of the angiotensin-converting enzyme/angiotensin II/angiotensin type 1 receptor (ACE/Ang-2/AT1R) axis in the process of MVPF. In addition, recombinant angiotensin-converting enzyme 2(rACE2), AT1R inhibitor valsartan, AGTR1-directed shRNA and ACE inhibitor perindopril were applied to verify the effect of inhibiting ACE/Ang-2/AT1R axis in the treatment of MVPF. Our study found MV induced an inflammatory reaction and collagen deposition in mouse lung tissue accompanied by the activation of ACE in lung tissue, increased concentration of Ang-2 in bronchoalveolar lavage fluid (BALF), and upregulation of AT1R in alveolar epithelial cells. The process of pulmonary fibrosis could be alleviated by the application of the ACE inhibitor perindopril, ATIR inhibitor valsartan and AGTR1-directed shRNA. Meanwhile, rACE2 could also alleviate MVPF through the degradation of Ang-2. Our finding indicated the ACE/Ang-2/AT1R axis played an essential role in the pathogenesis of MVPF. Pharmacological inhibition of the ACE/Ang-2/AT1R axis might be a promising strategy for the treatment of MVPF.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:131 |
|---|---|
| Enthalten in: |
International immunopharmacology - 131(2024) vom: 20. Apr., Seite 111855 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Feng, Jinhua [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 10.04.2024 Date Revised 10.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.intimp.2024.111855 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369833813 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369833813 | ||
| 003 | DE-627 | ||
| 005 | 20240410232719.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240318s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.intimp.2024.111855 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1371.xml |
| 035 | |a (DE-627)NLM369833813 | ||
| 035 | |a (NLM)38493697 | ||
| 035 | |a (PII)S1567-5769(24)00373-4 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Feng, Jinhua |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pharmacological inhibition of the ACE/Ang-2/AT1 axis alleviates mechanical ventilation-induced pulmonary fibrosis |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 10.04.2024 | ||
| 500 | |a Date Revised 10.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024. Published by Elsevier B.V. | ||
| 520 | |a Mechanical ventilation (MV) is an essential therapy for acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. However, it can also induce mechanical ventilation-induced pulmonary fibrosis (MVPF) and the underlying mechanism remains unknown. Based on a mouse model of MVPF, the present study aimed to explore the role of the angiotensin-converting enzyme/angiotensin II/angiotensin type 1 receptor (ACE/Ang-2/AT1R) axis in the process of MVPF. In addition, recombinant angiotensin-converting enzyme 2(rACE2), AT1R inhibitor valsartan, AGTR1-directed shRNA and ACE inhibitor perindopril were applied to verify the effect of inhibiting ACE/Ang-2/AT1R axis in the treatment of MVPF. Our study found MV induced an inflammatory reaction and collagen deposition in mouse lung tissue accompanied by the activation of ACE in lung tissue, increased concentration of Ang-2 in bronchoalveolar lavage fluid (BALF), and upregulation of AT1R in alveolar epithelial cells. The process of pulmonary fibrosis could be alleviated by the application of the ACE inhibitor perindopril, ATIR inhibitor valsartan and AGTR1-directed shRNA. Meanwhile, rACE2 could also alleviate MVPF through the degradation of Ang-2. Our finding indicated the ACE/Ang-2/AT1R axis played an essential role in the pathogenesis of MVPF. Pharmacological inhibition of the ACE/Ang-2/AT1R axis might be a promising strategy for the treatment of MVPF | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ACE/Ang-2/AT1R axis | |
| 650 | 4 | |a Mechanical ventilation | |
| 650 | 4 | |a Pharmacological treatment | |
| 650 | 4 | |a Pulmonary fibrosis | |
| 650 | 7 | |a Receptor, Angiotensin, Type 1 |2 NLM | |
| 650 | 7 | |a Peptidyl-Dipeptidase A |2 NLM | |
| 650 | 7 | |a EC 3.4.15.1 |2 NLM | |
| 650 | 7 | |a Perindopril |2 NLM | |
| 650 | 7 | |a Y5GMK36KGY |2 NLM | |
| 650 | 7 | |a Angiotensin-Converting Enzyme Inhibitors |2 NLM | |
| 650 | 7 | |a Valsartan |2 NLM | |
| 650 | 7 | |a 80M03YXJ7I |2 NLM | |
| 650 | 7 | |a RNA, Small Interfering |2 NLM | |
| 650 | 7 | |a Angiotensin II |2 NLM | |
| 650 | 7 | |a 11128-99-7 |2 NLM | |
| 700 | 1 | |a Huang, Xi |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Qiaoyi |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Ri |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Shaojie |e verfasserin |4 aut | |
| 700 | 1 | |a Xing, Shunpeng |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Mei, Shuya |e verfasserin |4 aut | |
| 700 | 1 | |a He, Zhengyu |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International immunopharmacology |d 2001 |g 131(2024) vom: 20. Apr., Seite 111855 |w (DE-627)NLM112639542 |x 1878-1705 |7 nnns |
| 773 | 1 | 8 | |g volume:131 |g year:2024 |g day:20 |g month:04 |g pages:111855 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.intimp.2024.111855 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 131 |j 2024 |b 20 |c 04 |h 111855 | ||