Age-Dependent Impairment of Reendothelialization After Arterial Injury

Gennaro, Giuseppa; Ménard, Catherine; Michaud, Sophie; Rivard, Alain

doi:10.1161/01.cir.0000050652.47145.4c

Cited by 72 publications

(43 citation statements)

References 20 publications

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“…This deficiency may be at the root of impaired neovascularization of ischemic tissues and attenuated re-endothelialization of injured tissues commonly observed in older patients. 68,69 Evidence for this hypothesis was provided by an elegant study by Eldeberg et al, 67 who showed that neovascularization of cardiac allografts in aged mice occurred only after transplantation of bone marrow-derived EPCs from young animals. Cardiovascular disease further compounds the effects of aging on EPC number and function.…”

Section: Epc and Agingmentioning

confidence: 99%

Therapeutic Potential of Endothelial Progenitor Cells in Cardiovascular Diseases

et al. 2005

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Abstract-Endothelial dysfunction and cell loss are prominent features in cardiovascular disease. Endothelial progenitor cells (EPCs) originating from the bone marrow play a significant role in neovascularization of ischemic tissues and in re-endothelialization of injured blood vessels. Several studies have shown the therapeutic potential of EPC transplantation in rescue of tissue ischemia and in repair of blood vessels and bioengineering of prosthetic grafts. Recent small-scale trials have provided preliminary evidence of feasibility, safety, and efficacy in patients with myocardial and critical limb ischemia. However, several studies have shown that age and cardiovascular disease risk factors reduce the availability of circulating EPCs (CEPCs) and impair their function to varying degrees. In addition, the relative scarcity of CEPCs limits the ability to expand these cells in sufficient numbers for some therapeutic applications. Priority must be given to the development of strategies to enhance the number and improve the function of CEPCs. Furthermore, alternative sources of EPC such as chord blood need to be explored. Strategies for improvement of cell adhesion, survival, and prevention of cell senescence are also essential to ensure therapeutic viability. Genetic engineering of EPCs may be a useful approach to developing these cells into efficient therapeutic tools. In the clinical arena there is pressing need to standardize the protocols for isolation, culture, and therapeutic application of EPC. Large-scale multi-center randomized trials are required to evaluate the long-term safety and efficacy of EPC therapy. Despite these hurdles, the outlook for EPC-based therapy for cardiovascular disease is promising. (Hypertension. 2005;46:7-18.)

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Section: Epc and Agingmentioning

confidence: 99%

Therapeutic Potential of Endothelial Progenitor Cells in Cardiovascular Diseases

et al. 2005

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“…14 Studies have shown that therapeutic application of VEGF is capable of reducing neointima formation in different in vivo models of acute arterial lesion formation. 2,[15][16][17] Delivery of recombinant VEGF protein has also been shown to accelerate the development of an intact luminal endothelial monolayer after stent implantation. Taken together, these data suggest that VEGF delivery might play an important therapeutic role after acute mechanical vascular injury, such as in percutaneous coronary interventions.…”

Section: See P 2283mentioning

confidence: 99%

Vascular Endothelial Growth Factor Regulates Reendothelialization and Neointima Formation in a Mouse Model of Arterial Injury

et al. 2004

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Background— The rate of reendothelialization is critical in neointima formation after arterial injury. Vascular endothelial growth factor (VEGF), a potent endothelial mitogen, has been advocated for accelerating endothelial repair and preventing intimal hyperplasia after percutaneous coronary interventions. However, the precise mechanism of action of VEGF treatment and the physiologic role of endogenous VEGF after arterial injury are not well described. To better understand the role of VEGF in arterial repair, we overexpressed both VEGF and a soluble, chimeric VEGF receptor (VEGF-trap), which binds free VEGF with high affinity, in a mouse model of arterial injury. Methods and Results— Four groups of C57BL/6 mice underwent denuding endothelial injury 1 day after systemic injection of recombinant adenovirus expressing (1) VEGF, (2) VEGF-trap, (3) VEGF plus VEGF-trap, or (4) control adenovirus. Circulating levels of adenovirus-encoded proteins were significantly elevated after gene transfer. VEGF overexpression accelerated reendothelialization and increased luminal endothelial cell proliferation 2 weeks after arterial injury ( P <0.05), resulting in decreased neointima formation at 4 weeks compared with control ( P <0.01). Cotreatment with VEGF-trap completely sequestered free VEGF and abrogated the beneficial effect of VEGF overexpression. Interestingly, sequestration of endogenous VEGF by VEGF-trap overexpression alone also led to delayed reendothelialization at 2 weeks ( P <0.01) and increased neointima formation at 4 weeks ( P <0.01). Conclusions— VEGF overexpression accelerated endothelial repair and inhibited neointima formation after arterial injury. Conversely, sequestration of exogenous and/or endogenous VEGF by VEGF-trap delayed reendothelialization and significantly increased neointima size. This demonstrates the therapeutic potential of VEGF but also emphasizes the important physiologic role of endogenous VEGF in vascular repair.

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“…Taking into account the duration of the regeneration process of the individual layers of a vessel wall after their mechanical injury [29][30][31] e.g. as a result of angioplasty, we can conclude that the time needed for partial regeneration of the arterial wall is approx.…”

Section: Discussionmentioning

confidence: 99%

Mechanical, rheological, fatigue, and degradation behavior of PLLA, PGLA and PDGLA as materials for vascular implants

et al. 2012

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The biggest challenge in the treatment of arterial stenosis remains the issue of optimization of stent design. Despite continuous improvement in surgical techniques and use of intensive pharmacotherapy, the results of stent coronary interventions may be unsatisfactory, and long-term interaction of a metal implant with a blood vessel results in complications such as recurrent stenosis and thrombosis. Therefore, it is necessary to search for new materials and stent designs to obtain a stent capable of restoring flow in the vessel and disappearing after fulfilling its function. Such stent must also be compatible with the vessel wall to enable regeneration of new structure of endothelium and deeper artery layers damaged during implantation. Consequently, there is ongoing search for functional solutions with minimum effects of long-term implant-tissue interaction. In light of the above, the team investigated the possibility of using biodegradable polymers already mentioned in the literature as a construction material for vascular stent. The study used three polyhydroxyacids based on lactic acid and glycolic acid: poly(l-lactide), poly(lactideco-glycolide) and poly(d,l-lactide-co-glycolide). The research focused on assessing changes in mechanical, thermomechanical, rheological, and fatigue properties during the process of hydrolytic degradation. The analysis also covered the rate of release of degradation products. The results of the conducted tests indicate the possibility of developing a vascular stent with biodegradable polymers.

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Age-Dependent Impairment of Reendothelialization After Arterial Injury

Cited by 72 publications

References 20 publications

Therapeutic Potential of Endothelial Progenitor Cells in Cardiovascular Diseases

Therapeutic Potential of Endothelial Progenitor Cells in Cardiovascular Diseases

Vascular Endothelial Growth Factor Regulates Reendothelialization and Neointima Formation in a Mouse Model of Arterial Injury

Mechanical, rheological, fatigue, and degradation behavior of PLLA, PGLA and PDGLA as materials for vascular implants

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