The prostacyclin analogue iloprost increases circulating endothelial progenitor cells in patients with critical limb ischemia

Stefano, Rossella Di; Barsotti, Maria Chiara; Melillo, Enrico; Iorio, Mariacarla; Santoni, Tatiana; Armani, Chiara; Dell’Omodarme, M.; Ristori, Chiara; Caterina, Raffaele De; Balbarini, Alberto

doi:10.1160/th07-08-0509

Cited by 41 publications

(31 citation statements)

References 33 publications

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“…In addition to the normal vascular supply promotion of the angiogenesis to the ischemic wound healing is necessary and can be observed by the levels of the VEGF in the molecular level. Di Stefano et al 6 reported that iloprost increased the levels of VEGF and promoted the angiogenesis in vivo so that the progenitor endothelial cell number expanded and ischemic limbs showed clinical improvement. We found that early administration of iloprost enhanced VEGF production in the tissue and there was a statistically significant increase compared to the control group (group 1 with iloprost therapy after ischemia vs. group 2 without iloprost therapy) (p=0.002) but there was no difference after 72 hours (p=0.6) Histopathologically increased levels of vascularization was observed in group 1 at 24 th hour that and although the increase was sustained even at 72 hours it was not statistically significant.…”

Section: Histopathological Resultsmentioning

confidence: 99%

“…Iloprost was also reported to have liver and kidney sparing properties in ischemia-reperfusion damage 4,5 . In patients with critical limb ischemia iloprost increased the endothelial progenitor cells in vivo and induced angiogenesis 6 . Iloprost was also reported by Lehman et al 7 that it has a protective effect against endotoxin induced intestinal damage in rats and that was attributed to the decrease in leucocyte adhesion in the circulation and decrease in oxitadive damage by inhibition of proinflammatory cytokines such as TNFalpha and IL-6 8,9 .…”

Section: Introductionmentioning

confidence: 97%

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Iloprost reduces colonic injury in ischemic colitis in rats

Karatepe¹,

Cakir²,

Ünal³

et al. 2011

Acta Cir. Bras.

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Purpose: Evaluate the effects of iloprost administration in the early period of ischemic colitis and the mechanism that how these effects develop. Methods: Thirty two Wistar albino female rats with an average weight of 220g were divided into four groups of eight rats. In group 1 the rats were given iloprost and sacrificed after 24 hours and in group 2 they were sacrificed after 24 hours without any iloprost. The rats in group 3 were administrated iloprost and sacrificed after 72 hours and in group 4 they were sacrificed at 72 th hour without iloprost. The differences between the groups as tissue damage, vascularization or apoptosis were assessed statistically. Results: Oxidative damage and apoptosis were less pronounced and vascularization was better developed in rats that were given iloprost and sacrificed at 24 th hour later in contrast to the rats that were not treated with iloprost. But there was no statistical difference among the groups at 72 th hour. Conclusion: Iloprost inhibited leucocyte infiltration, decreased proinflammatory cytokines and enhanced angiogenesis so that the oxidative stress and inflammatory response decreased resulting in lesser tissue damage. Key words: Colitis, Ischemic. Iloprost. Epoprostenol. Arachidonic Acid. Prostaglandins. Rats. RESUMOObjetivo: Avaliar os efeitos da administração de iloprosta no período precoce da colite isquêmica e o mecanismo da evolução destes efeitos. Métodos: Trinta e dois ratos Wistar fêmeas em torno de 220g foram distribuídos em quatro grupos de oito ratos. No grupo 1 administração de iloprosta e sacrificados após 24 horas; no grupo 2 foram sacrificados após 24 horas sem iloprosta; no grupo 3 foi administrado iloprosta e sacrificados após 72 horas; no grupo 4 foram sacrificados após 72 horas sem Iloprosta. As diferenças entre os grupos no referente a dano tecidual. vascularização ou apoptose foi apurada estatisticamente. Resultados: Dano oxidativo e apoptose foram menos acentuados e a vascularização foi melhor nos ratos que receberam iloprosta e sacrificados após 24 horas em contraste com os ratos que não receberam iloprosta. Porém, não houve diferença estatisticamente significante entre os grupos de 72 horas. Conclusão: Iloprosta inibe infiltração leucocitária, diminui a ação inflamatória de citoquinas e estimula angiogênese resultando em menor dano tecidual. Descritores: Colite Isquêmica. Iloprosta. Epoprostenol. Ácido Araquidônico. Prostaglandinas. Ratos.

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Section: Histopathological Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Iloprost reduces colonic injury in ischemic colitis in rats

Karatepe¹,

Cakir²,

Ünal³

et al. 2011

Acta Cir. Bras.

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“…Other medications, such as iloprost (prostacyclin, PGI2), cilostazol (phosphodiesterase-3 inhibitor) and others are widely used in CLI patients to relieve symptoms and signs of ischemia. Because iloprost increases the endothelial progenitor cell number in peripheral blood in vivo, it may have a direct effect on therapeutic angiogenesis (11,12).…”

Section: Discussionmentioning

confidence: 99%

A long term case study on therapeutic angiogenesis by transplantation of peripheral blood stem cells in critical limb ischemia after interventional revascularization

Reddy

Kwak²,

Shim³

et al. 2012

Diagn Interv Radiol

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Surgical and interventional revascularization in patients with critical limb ischemia (CLI) could prevent limb amputation, improve quality of life, and prolong survival. The limb salvage rate with direct revascularization is 82% over a four-year period, while indirect revascularization has a salvage rate of 64% (1, 2). However, as the affected arteries are mostly segmented, diffused, and located peripherally, the efficacy of surgical revascularization remains limited (3). Therefore, additional therapy, such as angiogenesis, is absolutely essential to improve the success of limb salvage.Therapeutic angiogenesis by intramuscular cell transplantation studies using autologous bone marrow mononuclear cells (BM-MNCs) (4, 5) and granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (PB-MNCs) (6) resulted in improvement in ankle brachial pressure index (ABPI), rest pain, transcutaneous oxygen pressure (TcPO 2 ), and pain-free walking distance in peripheral artery disease (PAD) patients with CLI. Comparative analysis between transplantation of BM-MNCs and G-CSF-mobilized PB-MNCs for patients with limb ischemia revealed no significant difference, thus PB-MNCs could be equally effective and more practical for treatment (7).Until now, there has been no report of a combinatorial approach of surgical or interventional revascularization and consecutive stem cell delivery, especially intra-arterial administration of G-CSF mobilized PBMNCs. In this case study, we investigated the long-term outcome and efficacy of PB-MNC therapy in an atherosclerotic CLI patient with interventional revascularization for four years. Case reportIn May 2007, we enrolled a 61-year-old male atherosclerotic PAD patient with a history of smoking, ischemic rest pain in the left leg, ischemic gangrene of the left fourth toe, erythematous swelling on the left foot (Fig. 1), and claudication of the right lower extremity. We assessed his left leg condition as Rutherford's grade III-category 5, and right leg as grade I-category 2. He had been treated for diabetes mellitus for 15 years and was taking insulin; he also had hypertension, ischemic heart disease, and a stent inserted in the left common iliac artery. All research protocols were approved by the institutional review board (IRB No. I2007016-74), and the patient provided informed consent for the procedure.Analysis was performed using computed tomography (CT) assisted angiography on a LightSpeed CT scanner (GE Healthcare, Milwaukee, Wisconsin, USA) and digital subtraction angiography using an Axiom Artis machine (Siemens Inc., Erlangen, Germany). The left superficial femoral artery (SFA) was found diffusely stenotic and completely occluded in the middle, through the collaterals, and the left popliteal artery INTERVENTIONAL RADIOLOGY CASE REPORTA long-term outcome of therapeutic angiogenesis by transplantation of peripheral blood stem cells in critical limb ischemia after interventional revascularization Alavala Matta Reddy, Byung Kook Kwak, Hyung Jin Shim, Eui-Chan J...

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“…The use of a biomarker, such as EPC, may be attractive and may help to identify RA patients at high risk for coronary artery disease, allowing for a more aggressive risk-reducing strategy. Equally exciting might be the promise of possibly manipulating EPC through stem cell treatment, perhaps reducing atherosclerotic burden in patients most at risk 22 . Further work in this area is clearly needed.…”

Section: Rheumatologymentioning

confidence: 99%