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Updated: Feb 11, 2026

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Fibulin-3 Attenuates Phosphate-Induced Vascular Smooth Muscle Cell Calcification by Inhibition of Oxidative Stress
Trang T D Luong1, Nadeshda Schelski1, Beate Boehme1
1Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Insights
Fibulin-3 protein effectively reduces vascular calcification in human aortic cells by inhibiting oxidative stress. This finding suggests Fibulin-3 may help treat vascular calcification in conditions like chronic kidney disease.
Area of Science:
- Biochemistry
- Vascular Biology
- Cell Biology
Background:
- Oxidative stress is a key factor in vascular calcification, particularly in chronic kidney disease (CKD) patients with hyperphosphatemia.
- Fibulin-3, an extracellular matrix glycoprotein, is known to inhibit oxidative stress and vascular remodeling.
Purpose of the Study:
- To investigate the impact of Fibulin-3 on phosphate-induced vascular calcification in human aortic smooth muscle cells (HAoSMCs).
Main Methods:
- Primary HAoSMCs were treated with phosphate-rich medium, with or without recombinant human Fibulin-3.
- Oxidative stress markers and osteo-/chondrogenic differentiation markers were analyzed.
- Hydrogen peroxide was used to mimic oxidative stress.
Main Results:
- Fibulin-3 significantly reduced calcium deposition in HAoSMCs exposed to phosphate.
- Fibulin-3 suppressed phosphate-induced alkaline phosphatase activity and the expression of osteogenic/chondrogenic markers.
- Fibulin-3 inhibited oxidative stress markers (NOX4, CYBA) and downstream effectors (PAI-1, MMP2, MMP9), while increasing antioxidant capacity.
Conclusions:
- Fibulin-3 attenuates phosphate-induced vascular calcification and osteo-/chondrogenic transdifferentiation by inhibiting oxidative stress.
- Increasing Fibulin-3 levels or supplementation could be a therapeutic strategy against vascular calcification in hyperphosphatemic conditions like CKD.
Background/Aims:
Fibulin-3, an extracellular matrix glycoprotein, inhibits vascular oxidative stress and remodeling in hypertension. Oxidative stress is prevalent in chronic kidney disease (CKD) patients and is an important mediator of osteo-/chondrogenic transdifferentiation and calcification of vascular smooth muscle cells (VSMCs) during hyperphosphatemia. Therefore, the present study explored the effects of Fibulin-3 on phosphate-induced vascular calcification.
Methods:
Experiments were performed in primary human aortic smooth muscle cells (HAoSMCs) treated with control or with phosphate without or with additional treatment with recombinant human Fibulin-3 protein or with hydrogen peroxide as an exogenous source of oxidative stress.
Results:
Treatment with calcification medium significantly increased calcium deposition in HAoSMCs, an effect significantly blunted by additional treatment with Fibulin-3. Moreover, phosphate-induced alkaline phosphatase activity and mRNA expression of osteogenic and chondrogenic markers MSX2, CBFA1, SOX9 and ALPL were all significantly reduced by addition of Fibulin-3. These effects were paralleled by similar regulation of oxidative stress in HAoSMCs. Phosphate treatment significantly up-regulated mRNA expression of the oxidative stress markers NOX4 and CYBA, down-regulated total antioxidant capacity and increased the expression of downstream effectors of oxidative stress PAI-1, MMP2 and MMP9 as well as BAX/BLC2 ratio in HAoSMCs, all effects blocked by additional treatment with Fibulin-3. Furthermore, the protective effects of Fibulin-3 on phosphate-induced osteogenic and chondrogenic markers expression in HAoSMCs were reversed by additional treatment with hydrogen peroxide.
Conclusions:
Fibulin-3 attenuates phosphate-induced osteo-/ chondrogenic transdifferentiation and calcification of VSMCs, effects involving inhibition of oxidative stress. Up-regulation or supplementation of Fibulin-3 may be beneficial in reducing the progression of vascular calcification during hyperphosphatemic conditions such as CKD.
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