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Updated: May 28, 2026

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Hyaluronan Regulates Vascular Smooth Muscle Cell Osteogenic Differentiation and Vascular Calcification
Shrea Roy1, Jamie Kane2,3, Irina Grigorieva1
1Wales Kidney Research Unit, Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
Insights
Hyaluronan (HA) regulates vascular calcification by influencing vascular smooth muscle cell (VSMC) differentiation. Targeting HA pathways offers a novel therapeutic strategy for preventing arterial calcification and cardiovascular mortality.
Area of Science:
- Biomedical Science
- Cardiovascular Research
- Cell Biology
Background:
- Vascular calcification is a significant risk factor for cardiovascular mortality.
- Vascular smooth muscle cell (VSMC) osteogenic differentiation drives calcification.
- Current treatments for vascular calcification are limited.
Purpose of the Study:
- To investigate the role of Hyaluronan (HA) in VSMC osteogenic differentiation.
- To explore HA as a potential therapeutic target for arterial calcification.
Main Methods:
- Human aortic VSMCs were treated with high phosphate and/or cytokines (IL6, TGF-β1).
- Gene and protein expression of HA-related molecules and osteogenic markers were analyzed.
- An in vivo mouse model of arterial calcification was utilized.
- Pharmacological and genetic manipulations of HA synthesis and degradation were performed.
Main Results:
- High phosphate/cytokine stimulation induced VSMC osteogenic differentiation, reduced HA deposition, and altered expression of HA synthases, hyaluronidases, and binding proteins.
- Similar changes were observed in a mouse model of arterial calcification.
- Modulating HA synthesis/degradation impacted VSMC osteogenic differentiation.
Conclusions:
- Hyaluronan (HA) and its associated proteins are key regulators of VSMC osteogenic differentiation and arterial calcification.
- HA represents a novel therapeutic target for treating vascular calcification.
Abstract:
Vascular calcification is a strong predictor of cardiovascular mortality and lacks effective treatment. The transformation of vascular smooth muscle cells (VSMCs) into osteoblast-like phenotypes is a key driver of calcification. This study identifies a regulatory role for Hyaluronan (HA) in VSMC osteogenic differentiation and arterial calcification. Human aortic VSMCs stimulated with high phosphate and/or pro-inflammatory cytokines (IL6 and TGF-β1) exhibited increased RUNX2, alkaline phosphatase and osteopontin expression, along with reduced contractility and elevated calcium deposition. This corresponded with reduced HA deposition and downregulation of HA synthase enzymes (HAS1, HAS2), Hyaluronidase enzymes (Hyal1), and HA binding proteins (CD44, TSG-6), whilst HAS3 and versican were upregulated. Comparable alterations in HA and protein expression were observed in an in vivo model of arterial calcification using vitamin K-deficient warfarin-fed mice. Pharmacological inhibition of HA synthesis, enzyme-mediated HA degradation and siRNA/plasmid modulation of HAS isoenzymes demonstrated a possible functional link between HA regulation and VSMC osteogenic differentiation. This study establishes HA and its associated binding proteins as key regulators of arterial calcification, highlighting a novel pathway for potential therapeutic intervention.
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