2. Academic Validation
  3. SNX17 knockdown improves post-ischemic angiogenesis via blocking lysosomal dependent VEGFR degradation

SNX17 knockdown improves post-ischemic angiogenesis via blocking lysosomal dependent VEGFR degradation

  • Life Sci. 2025 Sep 15:377:123739. doi: 10.1016/j.lfs.2025.123739.
Yang Tang 1,  Shiqi Tang 2,  Yue Chen 3,  Junkai Zhang 4,  Xueling Yu 3,  Pingyuan Mao 5,  Wei Wang 3,  Junyi Yu 3,  Feng Wang 6,  Chunyu Zeng 7
Affiliations

Affiliations

  • 1 Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China; Department of Cardiology, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease Research, Ministry of Education of China, Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology, Chongqing, China.
  • 2 Department of Cardiology, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China; State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, China.
  • 3 Department of Cardiology, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease Research, Ministry of Education of China, Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology, Chongqing, China.
  • 4 Department of Cardiology, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease Research, Ministry of Education of China, Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology, Chongqing, China; Department of Cardiology, Sichuan Armed Police Hospital, Sichuan, China.
  • 5 School of Clinical Medicine, Southwest Medical University, Luzhou 646000, Sichuan Province, China.
  • 6 Department of Cardiology, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease Research, Ministry of Education of China, Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology, Chongqing, China. Electronic address: f_wang01@163.com.
  • 7 Department of Cardiology, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease Research, Ministry of Education of China, Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology, Chongqing, China; State Key Laboratory of Trauma, Burns and Combined Injury, Daping Hospital, Third Military Medical University, Chongqing, China; Center of Chongqing College, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Chongqing, China; Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China. Electronic address: zengchunyu@tmmu.edu.cn.
PMID: 40412610 DOI: 10.1016/j.lfs.2025.123739
Abstract

The treatment options for critical limb ischemia (CLI) are limited, and existing methods are often ineffective in restoring microvascular blood supply. We recently explored the association of sorting nexin 17 (SNX17) with angiogenesis. Knockdown of SNX17 promotes angiogenesis and increased blood flow in hindlimb from hindlimb ischemia mice, accompanied with a higher limb salvage rate. This phenomenon can be attributed to the critical role of SNX17 in the degradation of some angiogenic factor receptors, including vascular endothelial growth factor receptor (VEGFR). The linkage between VEGFR and SNX17 facilitates its trafficking to lysosomal degradation. In the absence of SNX17, VEGFR accumulates in early endosomes, leading to prolonged and intensified activation, and consequently promoting angiogenesis. The current study shows that SNX17 plays an important role in angiogenesis by regulating the stability of angiogenic factor receptors, such as VEGFR, and presents a new strategy for facilitating tissue repair in ischemic environments.

Keywords

Angiogenesis; Critical limb ischemia; Degradation; SNX17; Vascular endothelial growth factor receptor.

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