Back to Search
Start Over
Targeted deletion of the inhibitory NF-kappaB p50 subunit in bone marrow-derived cells improves collateral growth after arterial occlusion.
- Source :
-
Cardiovascular research [Cardiovasc Res] 2010 Oct 01; Vol. 88 (1), pp. 179-85. Date of Electronic Publication: 2010 May 21. - Publication Year :
- 2010
-
Abstract
- Aims: Adaptive collateral artery growth (arteriogenesis) is an important mechanism to maintain tissue perfusion upon arterial obstruction. Leucocytes and inflammatory mediators play a crucial role in this process. Depletion of the nuclear factor kappa B (NF-κB) p50 subunit modulates inflammatory processes in cardiovascular disease. We hypothesized that NF-κB p50 is a regulator of the inflammatory response after arterial occlusion and subsequent collateral perfusion.<br />Methods and Results: Unilateral femoral artery ligation was performed in NF-κB p50-/- and wild-type (Wt, B6/129PF2) mice. Seven days after arterial occlusion, tissue perfusion restoration was significantly enhanced in NF-κB p50-/- mice compared with Wt mice (42.9 ± 3.9 vs. 32.0 ± 2.6% perfusion recovery, P = 0.04). Transplantation of NF-κB p50-/- bone marrow (bm) into Wt mice and vice versa showed that the effect of p50 subunit depletion can be predominantly attributed to the bone marrow-derived circulating cells (NF-κB p50-/- bm in Wt mice 42.1 ± 1.5%, Wt bm in NF-κB p50-/- mice 35.4±1.5% perfusion recovery). Histological analyses revealed a more elaborate extravasation of monocytes in hindlimb tissue of NF-κB p50-/- mice. Chemotaxis assays confirmed the increased migration ability of NF-κB p50-/- monocytes, which may be due to an observed increased integrin expression. Upon stimulation of blood from NF-κB p50-/- and Wt mice more interleukin-6 was produced, confirming the pro-inflammatory phenotype in absence of the p50 subunit.<br />Conclusion: Depletion of the NF-κB p50 subunit enhances collateral artery growth. Its absence in circulating cells improves tissue perfusion restoration after femoral artery ligation by increasing macrophage influx into the growing collateral vessels.
- Subjects :
- Animals
Arterial Occlusive Diseases genetics
Arterial Occlusive Diseases physiopathology
Bone Marrow Transplantation
Chemotaxis, Leukocyte
Disease Models, Animal
Female
Femoral Artery surgery
Inflammation Mediators blood
Interleukin-6 blood
Ligation
Macrophages immunology
Male
Mice
Mice, Knockout
Monocytes immunology
NF-kappa B p50 Subunit genetics
Time Factors
Arterial Occlusive Diseases immunology
Bone Marrow Cells immunology
Collateral Circulation
Gene Deletion
NF-kappa B p50 Subunit deficiency
Neovascularization, Physiologic
Subjects
Details
- Language :
- English
- ISSN :
- 1755-3245
- Volume :
- 88
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cardiovascular research
- Publication Type :
- Academic Journal
- Accession number :
- 20495189
- Full Text :
- https://doi.org/10.1093/cvr/cvq150