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Updated: Dec 1, 2025

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Indoxyl Sulfate-induced Vascular Calcification is mediated through Altered Notch Signaling Pathway in Vascular Smooth
Kazutoshi Yamaguchi1, Maimaiti Yisireyili1, Sumie Goto2
1Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Indoxyl sulfate induces vascular calcification by suppressing Notch signaling in aortic smooth muscle cells, leading to osteogenic differentiation and apoptosis. This study highlights Notch
Area of Science:
- Cardiovascular Biology
- Vascular Biology
- Molecular Medicine
Background:
- Vascular calcification (VC) is a complex process associated with cardiovascular disease.
- Indoxyl sulfate (IS) is a uremic toxin implicated in VC progression.
- The role of Notch signaling in IS-induced VC remains unclear.
Purpose of the Study:
- To investigate the role of Notch signaling in indoxyl sulfate (IS)-induced vascular calcification (VC).
- To examine the effects of IS on Notch pathway components and osteogenic markers in aortic smooth muscle cells (SMCs).
Main Methods:
- VC and molecular expression were assessed in rat models (DS, DH, DH+IS).
- Primary aortic SMCs were treated with IS to evaluate Notch receptor expression, apoptosis, and calcification.
- Pharmacological inhibition and genetic knockdown of Notch signaling were employed.
Main Results:
- IS-induced medial calcification in rat aortas and coronary arteries.
- IS suppressed Notch1, Notch3, and Hes-1 expression in a time- and dose-dependent manner.
- IS increased apoptosis and osteogenic marker expression in SMCs, while Notch inhibition or knockdown exacerbated these effects.
Conclusions:
- IS-induced VC is mediated by the suppression of Notch activity in aortic SMCs.
- This suppression promotes osteogenic differentiation and apoptosis, contributing to vascular calcification.
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