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Updated: Aug 6, 2026

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
Published on: September 14, 2021
Connective tissue growth factor is released from platelets under high shear stress and is differentially expressed in
Iwona Cicha1, Atilla Yilmaz, Yoji Suzuki
1Medical Clinic II, University of Erlangen-Nuremberg, Germany. Iwona_Cicha@yahoo.com
Insights
High shear stress releases connective tissue growth factor (CTGF) from platelets. This process, along with disturbed blood flow, may increase CTGF expression in atherosclerotic lesions, potentially driving disease progression.
Area of Science:
- Cardiovascular Biology
- Vascular Biology
- Atherosclerosis Research
Background:
- Connective tissue growth factor (CTGF) is elevated in atherosclerotic blood vessels.
- The precise mechanisms regulating CTGF in atherosclerosis remain unclear.
Purpose of the Study:
- To determine if high shear stress releases CTGF from human platelets.
- To investigate the relationship between local hemodynamics and CTGF expression in atherosclerotic lesions.
Main Methods:
- Human platelets were exposed to varying shear stress levels (10 or 120 dyn/cm2) and analyzed via Western blotting.
- Immunohistochemistry was used to assess endothelial CTGF expression in carotid plaque sections.
Main Results:
- High shear stress significantly increased CTGF release from platelets compared to low shear stress.
- Endothelial CTGF expression was notably higher in upstream regions of atherosclerotic vessels versus downstream regions.
- Neovascularization within plaques predominantly occurred in upstream areas.
Conclusions:
- High shear stress triggers CTGF release from platelets.
- Disturbed blood flow in atherosclerotic vessels may induce endothelial CTGF expression.
- These findings suggest a role for shear stress and hemodynamics in CTGF-mediated atherosclerosis progression.
Abstract:
Connective tissue growth factor (CTGF) is overexpressed in atherosclerotic blood vessels. To further investigate the role of CTGF in atherosclerosis, we examined whether CTGF is released from platelets by high shear stress, and whether the expression of CTGF along the atherosclerotic lesions depends on local hemodynamic conditions. Human platelets were subjected to 10 dyn/cm2 or 120 dyn/cm2 and analysed by Western blotting. Furthermore, longitudinal sections of 25 carotid plaques were immunohistochemically analysed for the endothelial expression of CTGF. A very low CTGF amount was secreted from platelets at low shear stress (11.4 +/- 3.9% of total CTGF in platelets). On the contrary, high shear stress caused a markedly increased CTGF release from platelets (29 +/- 13.8%, p = 0.07 vs low shear stress, n = 4). Immunohistochemical analyses showed that the mean numbers of CTGF-positive endothelial cells were significantly higher up-stream as compared with down-stream regions of the luminal surface of atherosclerotic vessels (21.3 +/- 3.6 vs 13.9 +/- 2.8 down-stream, p < 0.001). Moreover, in plaques undergoing intimal neovascularization, newly formed vessels accumulated particularly in up-stream parts of the lesions. In conclusion, this study demonstrated that CTGF is released from platelets by high shear stress. Furthermore, disturbed flow along atherosclerotic vessels may induce endothelial CTGF expression and contribute to the progress of atherosclerotic lesions.
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