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Aneurysm Is Restricted by CD34+ Cell-Formed Fibrous Collars Through the PDGFRb-PI3K Axis.

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  • 1Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

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CD34+ cells are crucial in abdominal aortic aneurysm (AAA) development. Non-bone marrow CD34+ cells transdifferentiate into myofibroblasts, contributing to fibrotic collars and AAA progression. Targeting this pathway may offer new therapeutic strategies for AAA.

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CD34+ cellsPDGFRbaneurysmsfibroblastsgenetic cell lineage tracings

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Area of Science:

  • Cardiovascular Biology
  • Stem Cell Research
  • Aortic Aneurysm Pathogenesis

Background:

  • Aortic aneurysm involves connective tissue imbalance.
  • CD34+ cells possess stem and progenitor properties.
  • The role of CD34+ cells in abdominal aortic aneurysm (AAA) is not well understood.

Purpose of the Study:

  • To investigate the role of CD34+ cells in AAA pathogenesis.
  • To identify the cellular origin and function of CD34+ cells in AAA.
  • To elucidate the molecular mechanisms regulating CD34+ cell involvement in AAA.

Main Methods:

  • Analysis of CD34 expression in human and mouse aortas.
  • Lineage tracing using Cd34-CreERT2;Rosa26-tdTomato;(Apoe-/-) models.
  • Bone marrow transplantation and single-cell sequencing.
  • Selective depletion of CD34+ cells and myofibroblasts.
  • Investigation of the PDGF-PDGFRb-PI3K signaling pathway.

Main Results:

  • CD34 expression is downregulated in aneurysmal aortas.
  • Non-bone marrow CD34+ cells transdifferentiate into Periostin+ myofibroblasts, forming fibrotic collars in AAA.
  • Depletion of CD34+ cells or myofibroblasts exacerbates AAA progression and mortality.
  • The PDGF-PDGFRb-PI3K axis is essential for myofibroblast generation from CD34+ cells.

Conclusions:

  • CD34+ cells, particularly non-bone marrow derived, play a critical role in AAA pathogenesis.
  • Transdifferentiation of CD34+ cells into Periostin+ myofibroblasts is a key mechanism in fibrotic collar formation.
  • The PDGF-PDGFRb-PI3K pathway represents a potential therapeutic target for AAA treatment.