Related Experiment Video
Updated: Jun 8, 2025
Implantation of a Carotid Cuff for Triggering Shear-stress Induced Atherosclerosis in Mice
Published on: January 13, 2012
PTP1B Modulates Carotid Plaque Vulnerability in Atherosclerosis Through Rab5-PDGFRβ-Mediated Endocytosis Disruption
Xiao Zhang1,2, Ran Xu1,2, Tao Wang1,2
1Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
Background:
Protein tyrosine phosphatase 1B (PTP1B) is a protein tyrosine phosphatase and modulates platelet-derived growth factor (PDGF)/platelet-derived growth factor receptor (PDGFR) signaling in vascular smooth muscle cells (VSMCs) via endocytosis. However, the related molecular pathways that participated in the interaction of endo-lysosome and the trafficking of PDGFR are largely unknown. This study aims to determine the subcellular regulating mechanism of PTP1B to the endo-lysosome degradation of PDGFR in atherosclerotic carotid plaques, thereby offering a potential therapeutic target for the stabilization of carotid plaques.
Methods:
The immunohistochemical staining technique was employed to assess the expression levels of both PDGFR-β and Caspase 3 in stable and vulnerable carotid plaques. Tunnel staining was utilized to quantify the apoptosis of carotid plaques. Live-cell imaging was employed to observe endocytic motility, while cell apoptosis was evaluated through Propidium Iodide staining. In an in vivo experiment, ApoE-/- mice were administered a PTP1B inhibitor to investigate the impact of PTP1B on atherosclerosis.
Results:
The heightened expression of PDGFR-β correlates with apoptosis in patients with vulnerable carotid plaques. At the subcellular level of VSMCs, PDGFR-β plays a pivotal role in sustaining a balanced endocytosis system motility, regulated by the expression of Rab5, a key regulator of endocytic motility. And PTP1B modulates PDGFR-β signaling via Rab5-mediated endocytosis. Additionally, disrupted endocytic motility influences the interplay between endosomes and lysosomes, which is crucial for controlling PDGFR-β trafficking. Elevated PTP1B expression induces cellular apoptosis and impedes migration and proliferation of carotid VSMCs. Ultimately, mice with PTP1B deficiency exhibit a reduction in atherosclerosis.
Conclusion:
Our results illustrate that PTP1B induces disruption in endocytosis and apoptosis of VSMCs through the Rab5-PDGFRβ pathway, suggesting a potential association with the heightened vulnerability of carotid plaques.
Insights
Protein tyrosine phosphatase 1B (PTP1B) disrupts endocytosis and promotes apoptosis in vascular smooth muscle cells (VSMCs) via the Rab5-PDGFRβ pathway. This finding offers a potential therapeutic target for stabilizing vulnerable carotid plaques.
Area of Science:
- Vascular Biology
- Cellular Signaling
- Atherosclerosis Research
Background:
- Protein tyrosine phosphatase 1B (PTP1B) modulates platelet-derived growth factor receptor (PDGFR) signaling in vascular smooth muscle cells (VSMCs) through endocytosis.
- The precise molecular mechanisms governing PDGFR trafficking and its interaction with the endo-lysosomal system in atherosclerosis remain largely undefined.
Purpose of the Study:
- To elucidate the subcellular regulatory role of PTP1B in the endo-lysosomal degradation of PDGFR within atherosclerotic carotid plaques.
- To identify PTP1B as a potential therapeutic target for stabilizing carotid plaques.
Main Methods:
- Immunohistochemical staining for PDGFR-β and Caspase 3 in carotid plaques.
- TUNEL and Propidium Iodide staining for apoptosis quantification.
- Live-cell imaging to observe endocytic motility.
- In vivo studies using ApoE-/- mice treated with a PTP1B inhibitor.
Main Results:
- Elevated PDGFR-β expression correlates with increased apoptosis in vulnerable carotid plaques.
- PTP1B modulates PDGFR-β signaling via Rab5-mediated endocytosis, impacting endosomal-lysosomal trafficking.
- Inhibition of PTP1B reduced atherosclerosis in ApoE-/- mice, while elevated PTP1B induced VSMC apoptosis and impaired function.
Conclusions:
- PTP1B disrupts VSMC endocytosis and promotes apoptosis through the Rab5-PDGFRβ pathway.
- This pathway is implicated in the increased vulnerability of carotid plaques, suggesting PTP1B as a therapeutic target.
More Related Videos
06:53A Rat Carotid Artery Pressure-Controlled Segmental Balloon Injury with Periadventitial Therapeutic Application
Published on: July 9, 2020
11:00A Model of Disturbed Flow-Induced Atherosclerosis in Mouse Carotid Artery by Partial Ligation and a Simple Method of RNA Isolation from Carotid Endothelium
Published on: June 22, 2010
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
01:12GPCR Desensitization