Accelerated vascular aging in CuZnSOD-deficient mice: impact on EPC function and reparative neovascularization.
<h4>Objective</h4>Aging is associated with increased oxidative stress levels and impaired neovascularization following ischemia. CuZnSOD has an important role to limit oxidative stress in the vasculature. Here we investigated the role of CuZnSOD for the modulation of ischemia-induced neo...
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0023308&type=printable |
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| author | Jessika Groleau Sylvie Dussault Julie Turgeon Paola Haddad Alain Rivard |
| author_facet | Jessika Groleau Sylvie Dussault Julie Turgeon Paola Haddad Alain Rivard |
| author_sort | Jessika Groleau |
| collection | DOAJ |
| description | <h4>Objective</h4>Aging is associated with increased oxidative stress levels and impaired neovascularization following ischemia. CuZnSOD has an important role to limit oxidative stress in the vasculature. Here we investigated the role of CuZnSOD for the modulation of ischemia-induced neovascularisation during aging.<h4>Methods and results</h4>Hindlimb ischemia was surgically induced in young (2- month-old) or older (8-month-old) wild type (WT) and CuZnSOD(-/-) mice. We found that blood flow recovery after ischemia and vascular density in ischemic muscles were significantly reduced in older compared to young WT mice. Both in young and older mice, CuZnSOD deficiency led to a further reduction of neovascularization. Accordingly, the resulting neovascularisation potential in a young CuZnSOD(-/-) mouse was similar to that of an older WT mouse. Oxidative stress levels were also increased to similar levels in the ischemic muscles of young CuZnSOD(-/-) and older WT mice. To identify potential mechanisms involved, we investigated the effect of aging and CuZnSOD deficiency on the number and the function of endothelial progenitor cells (EPCs). Both aging and CuZnSOD deficiency were associated with reduced number of bone marrow and peripheral EPCs. The effect of moderate aging alone on specific functional activities of EPCs (migration, integration into tubules) was modest. However, CuZnSOD deficiency was associated with severe age-dependent defects in EPC functional activities.<h4>Conclusions</h4>CuZnSOD deficiency is associated with accelerated vascular aging and impaired ischemia-induced neovascularization. Our results suggest that in the context of aging, CuZnSOD has an essential role to protect against excessive oxidative stress in ischemic tissues and preserve the function of EPCs. |
| format | Article |
| id | doaj-art-9dc4b1ebd967439190a60bba697e948e |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-9dc4b1ebd967439190a60bba697e948e2025-08-20T03:09:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0168e2330810.1371/journal.pone.0023308Accelerated vascular aging in CuZnSOD-deficient mice: impact on EPC function and reparative neovascularization.Jessika GroleauSylvie DussaultJulie TurgeonPaola HaddadAlain Rivard<h4>Objective</h4>Aging is associated with increased oxidative stress levels and impaired neovascularization following ischemia. CuZnSOD has an important role to limit oxidative stress in the vasculature. Here we investigated the role of CuZnSOD for the modulation of ischemia-induced neovascularisation during aging.<h4>Methods and results</h4>Hindlimb ischemia was surgically induced in young (2- month-old) or older (8-month-old) wild type (WT) and CuZnSOD(-/-) mice. We found that blood flow recovery after ischemia and vascular density in ischemic muscles were significantly reduced in older compared to young WT mice. Both in young and older mice, CuZnSOD deficiency led to a further reduction of neovascularization. Accordingly, the resulting neovascularisation potential in a young CuZnSOD(-/-) mouse was similar to that of an older WT mouse. Oxidative stress levels were also increased to similar levels in the ischemic muscles of young CuZnSOD(-/-) and older WT mice. To identify potential mechanisms involved, we investigated the effect of aging and CuZnSOD deficiency on the number and the function of endothelial progenitor cells (EPCs). Both aging and CuZnSOD deficiency were associated with reduced number of bone marrow and peripheral EPCs. The effect of moderate aging alone on specific functional activities of EPCs (migration, integration into tubules) was modest. However, CuZnSOD deficiency was associated with severe age-dependent defects in EPC functional activities.<h4>Conclusions</h4>CuZnSOD deficiency is associated with accelerated vascular aging and impaired ischemia-induced neovascularization. Our results suggest that in the context of aging, CuZnSOD has an essential role to protect against excessive oxidative stress in ischemic tissues and preserve the function of EPCs.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0023308&type=printable |
| spellingShingle | Jessika Groleau Sylvie Dussault Julie Turgeon Paola Haddad Alain Rivard Accelerated vascular aging in CuZnSOD-deficient mice: impact on EPC function and reparative neovascularization. PLoS ONE |
| title | Accelerated vascular aging in CuZnSOD-deficient mice: impact on EPC function and reparative neovascularization. |
| title_full | Accelerated vascular aging in CuZnSOD-deficient mice: impact on EPC function and reparative neovascularization. |
| title_fullStr | Accelerated vascular aging in CuZnSOD-deficient mice: impact on EPC function and reparative neovascularization. |
| title_full_unstemmed | Accelerated vascular aging in CuZnSOD-deficient mice: impact on EPC function and reparative neovascularization. |
| title_short | Accelerated vascular aging in CuZnSOD-deficient mice: impact on EPC function and reparative neovascularization. |
| title_sort | accelerated vascular aging in cuznsod deficient mice impact on epc function and reparative neovascularization |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0023308&type=printable |
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