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Updated: Mar 2, 2026
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Oligogalacturonic Acid Inhibits Vascular Calcification by Two Mechanisms: Inhibition of Vascular Smooth Muscle Cell
Ahmed Hodroge1, Eric Trécherel1, Marjorie Cornu1
1From the Unité INSERM U1088, CURS-Université de Picardie Jules Verne, Amiens, France (A.H., E.T., M.C., W.D., A.M., T.V., C.G., A.B., E.L., S.K., J.A.); Laboratoire de Biochimie, CHU Amiens, France (A.H., E.T., C.G., A.B., S.K., J.A.); Laboratoire de Glycochimie, des Antimicrobiens et des Agroressources LG2A UMR 7378, Université de Picardie Jules Verne, Amiens, France (K.A.-M., S.T., J.K.); Laboratoire des polysaccharides microbiens et végétaux EA3900-BIOPI, IUT Université de Picardie Jules Verne, Avenue des Facultés, Le Bailly, Amiens, France (R.E., J.C., E.P.); Sorbonne universités, Université de Technologie de Compiègne, CNRS, Laboratoire de Génie enzymatique et cellulaire, Rue Roger Couttolenc, CS 60319, Compiègne Cedex, France (C.S., C.R.); Laboratoire de Glycochimie des Antimicrobiens et des Agroressources, LG2A UMR 7378, Université de Picardie Jules Verne, Amiens Cedex 1, France (S.D.N., P.S.); and Service de Nephrologie, Hôpital Ambroise Paré, Assistance Publique Hôpitaux de Paris, Boulogne-Billancourt/Paris, Université Paris Ouest-Versailles-Saint-Quentin-en-Yvelines (UVSQ) et Inserm U1018, Equipe 5, CESP, Villejuif, France (Z.A.M.).
Insights
Oligogalacturonic acids, particularly DP8, significantly inhibit vascular calcification by preventing smooth muscle cell transformation into bone-like cells. This natural molecule also blocks key interactions in the calcification process.
Area of Science:
- Biochemistry
- Cell Biology
- Cardiovascular Research
Background:
- Cardiovascular diseases are a leading global cause of death.
- Vascular calcification, linked to diabetes, atherosclerosis, and kidney disease, contributes to cardiovascular morbidity and mortality.
- Vascular calcification is an active process involving vascular smooth muscle cell adaptation and extracellular vesicle-mediated mineralization.
Purpose of the Study:
- To identify novel natural molecules capable of inhibiting vascular calcification.
- To investigate the mechanism by which these molecules interfere with the calcification process.
Main Methods:
- In vitro assessment of oligogalacturonic acids on vascular smooth muscle cell calcification.
- Ex vivo evaluation of oligogalacturonic acids on isolated rat aortic ring calcification.
- Analysis of osteogenic marker expression and extracellular vesicle-collagen interactions.
Main Results:
- Oligogalacturonic acids reduced vascular smooth muscle cell calcification by 80% and aortic ring calcification by 50%.
- A specific oligogalacturonic acid (DP8) inhibited osteogenic marker expression, preventing smooth muscle cell transdifferentiation.
- DP8 was found to directly interact with extracellular vesicles and mask the GFOGER sequence on type I collagen.
Conclusions:
- DP8 effectively inhibits vascular calcification primarily by suppressing osteogenic differentiation.
- DP8 also contributes to inhibition by preventing extracellular vesicle binding to type I collagen.
- Oligogalacturonic acids represent a promising natural therapeutic strategy for vascular calcification.
Objective:
Cardiovascular diseases constitute the leading cause of mortality worldwide. Calcification of the vessel wall is associated with cardiovascular morbidity and mortality in patients having many diseases, including diabetes mellitus, atherosclerosis, and chronic kidney disease. Vascular calcification is actively regulated by inductive and inhibitory mechanisms (including vascular smooth muscle cell adaptation) and results from an active osteogenic process. During the calcification process, extracellular vesicles (also known as matrix vesicles) released by vascular smooth muscle cells interact with type I collagen and then act as nucleating foci for calcium crystallization. Our primary objective was to identify new, natural molecules that inhibit the vascular calcification process.
Approach And Results:
We have found that oligogalacturonic acids (obtained by the acid hydrolysis of polygalacturonic acid) reduce in vitro inorganic phosphate-induced calcification of vascular smooth muscle cells by 80% and inorganic phosphate-induced calcification of isolated rat aortic rings by 50%. A specific oligogalacturonic acid with a degree of polymerization of 8 (DP8) was found to inhibit the expression of osteogenic markers and, thus, prevent the conversion of vascular smooth muscle cells into osteoblast-like cells. We also evidenced in biochemical and immunofluorescence assays a direct interaction between matrix vesicles and type I collagen via the GFOGER sequence (where single letter amino acid nomenclature is used, O=hydroxyproline) thought to be involved in interactions with several pairs of integrins.
Conclusions:
DP8 inhibits vascular calcification development mainly by inhibition of osteogenic marker expression but also partly by masking the GFOGER sequence-thereby, preventing matrix vesicles from binding to type I collagen.
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