Myeloid ALX/FPR2 regulates vascularization following tissue injury
Ischemic injury initiates a sterile inflammatory response that ultimately participates in the repair and recovery of tissue perfusion. Macrophages are required for perfusion recovery during ischemia, in part because they produce growth factors that aid in vascular remodeling. The input signals governing this pro-revascularization phenotype remain of interest. Here we found that hindlimb ischemia increases levels of resolvin D1 (RvD1), an inflammation-resolving lipid mediator that targets macrophages via its receptor, ALX/FPR2. Exogenous RvD1 enhances perfusion recovery during ischemia, and mice deficient in Alx/Fpr2 have an endogenous defect in this process. Mechanistically, RNA sequencing revealed that RvD1 induces a transcriptional program in macrophages characteristic of a pro-revascularization phenotype. Vascularization of ischemic skeletal muscle, as well as cutaneous wounds, is impaired in mice with myeloid-specific deficiency of Alx/Fpr2, and this is associated with altered expression of pro-revascularization genes in skeletal muscle and macrophages isolated from skeletal muscle. Collectively, these results uncover a role of ALX/FPR2 in revascularization that may be amenable to therapeutic targeting in diseases associated with altered tissue perfusion and repair.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:117 |
|---|---|
| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 117(2020), 25 vom: 23. Juni, Seite 14354-14364 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Sansbury, Brian E [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 28.08.2020 Date Revised 14.02.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1073/pnas.1918163117 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM310931614 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM310931614 | ||
| 003 | DE-627 | ||
| 005 | 20240214232218.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1073/pnas.1918163117 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1292.xml |
| 035 | |a (DE-627)NLM310931614 | ||
| 035 | |a (NLM)32513697 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Sansbury, Brian E |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Myeloid ALX/FPR2 regulates vascularization following tissue injury |
| 264 | 1 | |c 2020 | |
| 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 28.08.2020 | ||
| 500 | |a Date Revised 14.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Ischemic injury initiates a sterile inflammatory response that ultimately participates in the repair and recovery of tissue perfusion. Macrophages are required for perfusion recovery during ischemia, in part because they produce growth factors that aid in vascular remodeling. The input signals governing this pro-revascularization phenotype remain of interest. Here we found that hindlimb ischemia increases levels of resolvin D1 (RvD1), an inflammation-resolving lipid mediator that targets macrophages via its receptor, ALX/FPR2. Exogenous RvD1 enhances perfusion recovery during ischemia, and mice deficient in Alx/Fpr2 have an endogenous defect in this process. Mechanistically, RNA sequencing revealed that RvD1 induces a transcriptional program in macrophages characteristic of a pro-revascularization phenotype. Vascularization of ischemic skeletal muscle, as well as cutaneous wounds, is impaired in mice with myeloid-specific deficiency of Alx/Fpr2, and this is associated with altered expression of pro-revascularization genes in skeletal muscle and macrophages isolated from skeletal muscle. Collectively, these results uncover a role of ALX/FPR2 in revascularization that may be amenable to therapeutic targeting in diseases associated with altered tissue perfusion and repair | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a ischemia | |
| 650 | 4 | |a macrophages | |
| 650 | 4 | |a resolvins | |
| 650 | 7 | |a FPR2 protein, human |2 NLM | |
| 650 | 7 | |a Receptors, Formyl Peptide |2 NLM | |
| 650 | 7 | |a Receptors, Lipoxin |2 NLM | |
| 650 | 7 | |a formyl peptide receptor 2, mouse |2 NLM | |
| 650 | 7 | |a resolvin D1 |2 NLM | |
| 650 | 7 | |a Docosahexaenoic Acids |2 NLM | |
| 650 | 7 | |a 25167-62-8 |2 NLM | |
| 700 | 1 | |a Li, Xiaofeng |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Blenda |e verfasserin |4 aut | |
| 700 | 1 | |a Patsalos, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Giannakis, Nikolas |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Michael J |e verfasserin |4 aut | |
| 700 | 1 | |a Nagy, Laszlo |e verfasserin |4 aut | |
| 700 | 1 | |a Spite, Matthew |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Proceedings of the National Academy of Sciences of the United States of America |d 1915 |g 117(2020), 25 vom: 23. Juni, Seite 14354-14364 |w (DE-627)NLM000008982 |x 1091-6490 |7 nnns |
| 773 | 1 | 8 | |g volume:117 |g year:2020 |g number:25 |g day:23 |g month:06 |g pages:14354-14364 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1073/pnas.1918163117 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 117 |j 2020 |e 25 |b 23 |c 06 |h 14354-14364 | ||