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

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

  • Adv Sci (Weinh). 2024 Dec 27:e2408996. doi: 10.1002/advs.202408996.
Hong Wu 1,  Xiaoping Yang 2,  Ting Chen 1,  Baoqi Yu 3,  Mengjia Chen 1,  Ting Wang 1,  Liujun Jiang 1,  Bohuan Zhang 1,  Xuhao Zhou 1,  Junning Cheng 1,  Kai Chen 1,  Tao Zhang 4,  Yanhua Hu 1,  Simon Xu 5,  Jiangfang Lian 2,  Hongkun Zhang 6,  Qingzhong Xiao 7,  Honghua Ye 2,  Qingbo Xu 1
Affiliations

Affiliations

  • 1 Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
  • 2 Department of Cardiology, Ningbo Institute of Innovation for Combined Medicine and Engineering, Lihuili Hospital Affiliated to Ningbo University, Ningbo University, Ningbo, Zhejiang, 315000, China.
  • 3 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Key Laboratory of Metabolic Disorder-Related Cardiovascular Diseases, Beijing, 100069, China.
  • 4 Department of Vascular Surgery, Peking University People's Hospital, Beijing, 100044, China.
  • 5 Department of Surgery, Liverpool Heart and Chest Hospital, Liverpool, L14 3PE, UK.
  • 6 Department of Vascular Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
  • 7 Centre for Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
PMID: 39731355 DOI: 10.1002/advs.202408996
Abstract

Aortic aneurysm is a life-threatening disease caused by progressive dilation of the aorta and weakened aortic walls. Its pathogenesis involves an imbalance between connective tissue repair and degradation. CD34+ cells comprise a heterogeneous population that exhibits stem cell and progenitor cell properties. However, the role of CD34+ cells in abdominal aortic aneurysm (AAA) remains unclear. In this study, downregulated CD34 expression is observed in aneurysmal aortas from both patients and mouse models compared to that in non-dilated aortas. Furthermore, by combining Cd34-CreERT2;Rosa26-tdTomato;(apoE-/-) lineage tracing, bone marrow transplantation, and single-cell Sequencing, it is found that during AAA development, non-bone marrow CD34+ cells are activated to transdifferentiate into Periostin+ myofibroblasts, thereby contributing to the formation of fibrotic collars. Dual recombinase-based lineage tracing confirms the presence and involvement of CD34+/Periostin+ myofibroblasts in fibrotic collar formation during AAA development. Functionally, selective depletion of systemic or non-bone marrow CD34+ cells, as well as CD34+/Periostin+ myofibroblasts, by diphtheria toxin significantly exacerbates AAA progression and increases disease mortality. Mechanistically, it is identified that the PDGF-PDGFRb-PI3K axis is indispensable for Periostin+ myofibroblast generation from non-bone marrow CD34+ cells in AAA, offering a new therapeutic target for patients with AAA at a high risk of rupture.

Keywords

CD34+ cells; PDGFRb; aneurysms; fibroblasts; genetic cell lineage tracings.

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