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HTATIP2 regulates arteriogenic activity in monocytes from patients with limb ischemia.
Patel, Ashish S; Ludwinski, Francesca E; Mondragon, Angeles; Nuthall, Katherine; Saha, Prakash; Lyons, Oliver; Squadrito, Mario Leonardo; Siow, Richard; De Palma, Michele; Smith, Alberto; Modarai, Bijan.
Afiliación
  • Patel AS; Academic Department of Vascular Surgery, South Bank Section, School of Cardiovascular and Metabolic Medicine & Sciences, King's BHF Centre of Research Excellence, King's College London, United Kingdom.
  • Ludwinski FE; Academic Department of Vascular Surgery, South Bank Section, School of Cardiovascular and Metabolic Medicine & Sciences, King's BHF Centre of Research Excellence, King's College London, United Kingdom.
  • Mondragon A; Academic Department of Vascular Surgery, South Bank Section, School of Cardiovascular and Metabolic Medicine & Sciences, King's BHF Centre of Research Excellence, King's College London, United Kingdom.
  • Nuthall K; Academic Department of Vascular Surgery, South Bank Section, School of Cardiovascular and Metabolic Medicine & Sciences, King's BHF Centre of Research Excellence, King's College London, United Kingdom.
  • Saha P; Academic Department of Vascular Surgery, South Bank Section, School of Cardiovascular and Metabolic Medicine & Sciences, King's BHF Centre of Research Excellence, King's College London, United Kingdom.
  • Lyons O; Academic Department of Vascular Surgery, South Bank Section, School of Cardiovascular and Metabolic Medicine & Sciences, King's BHF Centre of Research Excellence, King's College London, United Kingdom.
  • Squadrito ML; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Siow R; Department of Vascular Biology and Inflammation, South Bank Section, School of Cardiovascular and Metabolic Medicine & Sciences, King's BHF Centre of Research Excellence, King's College London, United Kingdom.
  • De Palma M; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Smith A; Academic Department of Vascular Surgery, South Bank Section, School of Cardiovascular and Metabolic Medicine & Sciences, King's BHF Centre of Research Excellence, King's College London, United Kingdom.
  • Modarai B; Academic Department of Vascular Surgery, South Bank Section, School of Cardiovascular and Metabolic Medicine & Sciences, King's BHF Centre of Research Excellence, King's College London, United Kingdom.
JCI Insight ; 8(24)2023 Dec 22.
Article en En | MEDLINE | ID: mdl-37847559
Use of autologous cells isolated from elderly patients with multiple comorbidities may account for the modest efficacy of cell therapy in patients with chronic limb threatening ischemia (CLTI). We aimed to determine whether proarteriogenic monocyte/macrophages (Mo/MΦs) from patients with CLTI were functionally impaired and to demonstrate the mechanisms related to any impairment. Proarteriogenic Mo/MΦs isolated from patients with CLTI were found to have an impaired capacity to promote neovascularization in vitro and in vivo compared with those isolated from healthy controls. This was associated with increased expression of human HIV-1 TAT interactive protein-2 (HTATIP2), a transcription factor known to suppress angiogenesis/arteriogenesis. Silencing HTATIP2 restored the functional capacity of CLTI Mo/MΦs, which was associated with increased expression of arteriogenic regulators Neuropilin-1 and Angiopoietin-1, and their ability to enhance angiogenic (endothelial tubule formation) and arteriogenic (smooth muscle proliferation) processes in vitro. In support of the translational relevance of our findings, silencing HTATIP2 in proarteriogenic Mo/MΦs isolated from patients with CLTI rescued their capacity to enhance limb perfusion in the ischemic hindlimb by effecting greater angiogenesis and arteriogenesis. Ex vivo modulation of HTATIP2 may offer a strategy for rescuing the functional impairment of pro-angio/arteriogenic Mo/MΦs prior to autologous delivery and increase the likelihood of clinical efficacy.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Monocitos / Neovascularización Fisiológica Límite: Aged / Animals / Humans Idioma: En Revista: JCI Insight Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Monocitos / Neovascularización Fisiológica Límite: Aged / Animals / Humans Idioma: En Revista: JCI Insight Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido