HTATIP2 regulates arteriogenic activity in monocytes from patients with limb ischemia.

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  • Additional Information
    • Source:
      Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE
    • Publication Information:
      Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]-
    • Subject Terms:
      Monocytes*/metabolism ; Neovascularization, Physiologic*; Animals ; Mice ; Humans ; Aged ; Collateral Circulation ; Muscle, Skeletal/metabolism ; Mice, Knockout ; Ischemia/metabolism ; Transcription Factors ; Acetyltransferases
    • Abstract:
      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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    • Contributed Indexing:
      Keywords: Angiogenesis; Cardiovascular disease; Macrophages; Monocytes; Therapeutics
    • Accession Number:
      0 (Transcription Factors)
      EC 2.3.1.48 (HTATIP2 protein, human)
      EC 2.3.1.- (Acetyltransferases)
    • Publication Date:
      Date Created: 20231017 Date Completed: 20231225 Latest Revision: 20241023
    • Publication Date:
      20241023
    • Accession Number:
      PMC10807724
    • Accession Number:
      10.1172/jci.insight.131419
    • Accession Number:
      37847559