Abstract
ObjectiveAging 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.Methods and ResultsHindlimb 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.ConclusionsCuZnSOD 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.
Highlights
In patients with cardiovascular diseases, the capacity of the organism to develop new blood vessels constitutes an important adaptive mechanism against ischemia [1]
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 endothelial progenitor cells (EPCs)
Summary
In patients with cardiovascular diseases, the capacity of the organism to develop new blood vessels (neovascularization) constitutes an important adaptive mechanism against ischemia [1]. It has been demonstrated that circulating EPCs in adults can home to ischemic tissues and contribute to the formation of new blood vessels [4]. Advanced age is a major risk factor for coronary and peripheral artery disease. One of the consequences of aging is a decline in the ability of the organism to respond to different stresses, including ischemia. Advanced age is associated with a defect in neovessel formation following arterial occlusion in different animal models [5,6]. The precise mechanisms involved in the modulation of neovascularisation and EPC function by aging remain to be determined
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
