Aneurysm Is Restricted by CD34+ Cell‐Formed Fibrous Collars Through the PDGFRb‐PI3K Axis
Year: 2024
Type: article
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.
Source: Advanced Science
Authors: Hong Wu, Xiaoping Yang, Ting Chen, Baoqi Yu, Mengjia Chen, Ting Wang, Liujun Jiang, Bohuan Zhang, Xuhao Zhou, Junning Cheng, Kai Chen, Tao Zhang, Yanhua Hu, Simon Xu, Jiangfang Lian, Hongkun Zhang, Qingzhong Xiao, Honghua Ye, Qingbo Xu
Institutions: First Affiliated Hospital Zhejiang University, Zhejiang University, Ningbo University, Ningbo Medical Center Lihuili Hospital, Capital Medical University, Peking University People's Hospital, Liverpool Heart and Chest Hospital, Queen Mary University of London, William Harvey Research Institute
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,120
Awards: 高血压诱导的心肌重塑中CD34+细胞分化与代谢改变的关系及机理研究, G3361490508, G3425524147, A novel role for CD34+ cell-derived fibroblasts in abdominal aortic aneurysm, G4812357902, G4917887423, G5764821208, 代谢调控血管外膜干/祖细胞参与血管重塑的作用及机制研究, CD34+干/祖细胞异质性调控血管纤维重塑参与血管硬化的新机制, G6289672498, A novel role of Cezanne in vascular smooth muscle cell proliferation and neointima hyperplasia, Functional roles of hnRNPA1 in vascular smooth muscle cell phenotype modulation and neointima hyperplasia, G7862607268, G8663492048
OpenAlex ID: W4405854919