Therapeutic Angiogenesis in the Management of Critical Limb Ischemia

Attanasio, Steve; Snell, Jeffrey

doi:10.1097/crd.0b013e318199e9b7

Cited by 66 publications

(47 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The activation of these receptors leads to EC proliferation and migration and the sprouting of new capillaries, which constitutes the process of neovascularization within the tissue, relieving the ischemic burden. As such, the VEGF-VEGFR signaling axis has been extensively explored toward the treatment of ischemic disease (71), with the goal of increasing collateral vessel density, thus providing increased blood flow to ischemic tissues (2). A number of factors are critical in rendering the extracellular VEGF signal to an intracellular response, but none is more Fig.…”

Section: Cd31mentioning

confidence: 99%

Endothelial cell-by-cell profiling reveals the temporal dynamics of VEGFR1 and VEGFR2 membrane localization after murine hindlimb ischemia

Imoukhuede

Dokun

Annex

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Imoukhuede PI, Dokun AO, Annex BH, Popel AS. Endothelial cell-by-cell profiling reveals the temporal dynamics of VEGFR1 and VEGFR2 membrane localization after murine hindlimb ischemia. Am J Physiol Heart Circ Physiol 304: H1085-H1093, 2013. First published February 1, 2013 doi:10.1152/ajpheart.00514.2012 cell surface localization plays a critical role in transducing VEGF signaling toward angiogenic outcomes, and quantitative characterization of these parameters is critical to advancing computational models for predictive medicine. However, studies to this point have largely examined intact muscle; thus, essential data on the cellular localization of the receptors within the tissue are currently unknown. Therefore, our aims were to quantitatively analyze VEGFR localization on endothelial cells (ECs) from mouse hindlimb skeletal muscles after the induction of hindlimb ischemia, an established model for human peripheral artery disease. Flow cytometry was used to measure and compare the ex vivo surface localization of VEGFR1 and VEGFR2 on CD31 ϩ /CD34 ϩ ECs 3 and 10 days after unilateral ligation of the femoral artery. We determined that 3 days after hindlimb ischemia, VEGFR2 surface levels were decreased by 80% compared with ECs from the nonischemic limb; 10 days after ischemia, we observed a twofold increase in surface levels of the modulatory receptor, VEGFR1, along with increased proliferating cell nuclear antigen, urokinase plasminogen activator, and urokinase plasminogen activator receptor mRNA expression compared with the nonischemic limb. The significant upregulation of VEGFR1 surface levels indicates that VEGFR1 indeed plays a critical role in the ischemia-induced perfusion recovery process, a process that includes both angiogenesis and arteriogenesis. The quantification of these dissimilarities, for the first time ex vivo, provides insights into the balance of modulatory (VEGFR1) and proangiogenic (VEGFR2) receptors in ischemia and lays the foundation for systems biology approaches toward therapeutic angiogenesis.angiogenesis; peripheral artery disease; endothelial cells; skeletal muscle; quantitative flow cytometry; receptor localization; Quantibrite; hindlimb ischemia; vascular endothelial growth factor receptor THE VEGF RECEPTOR (VEGFR)-ligand family is a key regulator of angiogenesis, the growth of new blood vessels from preexisting microvasculature. VEGF binding to its receptors activates intracellular signaling pathways inducing the endothelial proliferation and migration necessary for angiogenesis. Therapeutic angiogenesis aims to treat ischemic disease through the supplementation of VEGF and/or other angiogenic growth factors (31,48). The use of VEGF has successfully stimulated neovascularization in animal models of ischemia (30, 68). However, the use of VEGFs, fibroblast growth factor, hepatocyte growth factor, and other proangiogenic molecules has not yielded successful clinical outcomes (8,31,34). These clinical setbacks have been attributed to inadequate dosing, duration, and delivery as well a...

show abstract

Section: Cd31mentioning

confidence: 99%

Endothelial cell-by-cell profiling reveals the temporal dynamics of VEGFR1 and VEGFR2 membrane localization after murine hindlimb ischemia

Imoukhuede

Dokun

Annex

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…After 2 years, only 40 % of those fitted with prosthesis can ambulate, and even fewer are independent outside the home. Despite advances in vascular and endovascular techniques, 14-20 % of patients with chronic lower limb ischemia will not be eligible for distal arterial reconstruction due to occlusion of crural and pedal vessels (Attanasio and Snell 2009). Because of this generally poor outcome, there is a strong need for attempting any procedure to save the affected limb (Casamassimi et al 2012;Inderbitzi et al 1992).…”

Section: Introductionmentioning

confidence: 99%

Autologous transplantation of CD34+ bone marrow derived mononuclear cells in management of non-reconstructable critical lower limb ischemia

et al. 2014

View full text Add to dashboard Cite

Patients with a decrease in limb perfusion with a potential threat to limb viability manifested by ischemic rest pain, ischemic ulcers, and/or gangrene are considered to have critical limb ischemia (CLI). Because of this generally poor outcome, there is a strong need for attempting any procedure to save the affected limb. The aim of this work is to evaluate the possibility to use stem cell therapy as a treatment option for patients with chronic critical lower limb ischemia with no distal run off. This study includes 20 patients with chronic critical lower limb ischemia with no distal run off who are unsuitable for vascular or endovascular option. These patients underwent stem cell therapy (SCT) by autologous transplantation of bone marrow derived mononuclear cells. 55 % of patients treated with SCT showed improvement of the rest pain after the first month, 60 % continued improvement of the rest pain after 6 months, 75 % after 1 year and 80 % after 2 years and continued without any deterioration till the third year. Limb salvage rate after STC was 80 % after the first year till the end of the second and third years. SCT can result in angiogenesis in patients with no-option CLI, providing a foundation for the application of this therapy to leg ischemia.

show abstract

“…[19][20][21] These combination gene therapies are currently being examined in animal models in preparation for translation to clinical human therapy. 22 Thus, identification and use of maturation factors are required to achieve optimal therapeutic angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Apelin induces enlarged and nonleaky blood vessels for functional recovery from ischemia

Kidoya

Naito

Takakura

2010

Blood

107

102

View full text Add to dashboard Cite

The efficacy of therapeutic angiogenesis for revascularization in ischemia using genes, proteins, and cells has been established. For further improvement, processes allowing enlargement of the luminal cavity to facilitate efficient blood flow need to be facilitated. Recently, we found that expression of APJ and its specific ligand, apelin, is seen in endothelial cells when angiogenesis is taking place during embryogenesis. Apelin-deficient mice are viable but have narrow intersomitic ves-

show abstract

Therapeutic Angiogenesis in the Management of Critical Limb Ischemia

Cited by 66 publications

References 57 publications

Endothelial cell-by-cell profiling reveals the temporal dynamics of VEGFR1 and VEGFR2 membrane localization after murine hindlimb ischemia

Endothelial cell-by-cell profiling reveals the temporal dynamics of VEGFR1 and VEGFR2 membrane localization after murine hindlimb ischemia

Autologous transplantation of CD34+ bone marrow derived mononuclear cells in management of non-reconstructable critical lower limb ischemia

Apelin induces enlarged and nonleaky blood vessels for functional recovery from ischemia

Contact Info

Product

Resources

About