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Updated: Apr 15, 2026

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
CALU polymorphism A29809G affects calumenin availability involving vascular calcification
Eva Jover1, Francisco Marín1, Míriam Quintana1
1Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain.
Abstract:
Calumenin inhibits gamma-carboxylation of matrix-Gla-protein preventing BMP2-dependent calcification. Our aim was to explore the clinical relevance and functionality of the CALU polymorphism rs1043550, and the relationship of calumenin time-dependent expression profile with the active calcification of human vascular smooth muscle cells (hVSMC). Coronary artery calcium score and lesion severity were assessed by cardiac computed tomography in 139 consecutive low-risk patients genotyped for rs1043550. Polymorphic (G) allele carriage was associated with lower calcium (OR: 6.19, p=0.042). Calcified arteries from CALU 'A' allele carriers undergoing cardiovascular surgery exhibited higher residual calcification, higher calumenin immunostaining and lower matrix-Gla-protein, contrary to 'G' allele carriers. In a luciferase reporter system in vascular cells, polymorphic 'G' allele reduced the mRNA stability by 30% (p < 0.05). Osteogenic high-phosphate media induced active differentiation of hVSMC onto functional osteoblast-like cells as demonstrated by extracellular matrix mineralization and osteoblast markers expression. Calumenin was early over-expressed at day 3 (p < 0.05), but decreased thereafter (mRNA and protein) with implications on gamma-carboxylation system. Calumenin was found released and co-localizing with extracellular matrix calcifications. The CALU polymorphism rs1043550 affects mRNA stability and tissue availability of calumenin thus supporting the protective clinical significance. Calumenin shows a time-dependent profile during induced calcification. These data demonstrate a novel association of vascular calcification with the VSMC phenotypic transition into osteoblast-like cells. Moreover, hyperphosphatemic stimuli render calumenin accumulation in the mineralized extracellular matrix.
Insights
Calumenin (CALU) gene variants influence vascular calcification by affecting protein levels and matrix-Gla-protein activity. This study links a specific CALU polymorphism to reduced arterial calcification, highlighting its clinical significance.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Biochemistry
Background:
- Calumenin (CALU) inhibits matrix-Gla-protein (MGP) gamma-carboxylation, a process crucial for preventing vascular calcification.
- Vascular calcification is a significant risk factor for cardiovascular disease, involving complex cellular and molecular mechanisms.
Purpose of the Study:
- To investigate the clinical relevance of the CALU gene polymorphism rs1043550.
- To explore the functional impact of this polymorphism on calumenin expression and activity.
- To elucidate the relationship between calumenin expression profiles and vascular smooth muscle cell (hVSMC) calcification.
Main Methods:
- Genotyping of 139 low-risk patients for CALU rs1043550.
- Cardiac computed tomography (CT) to assess coronary artery calcium score and lesion severity.
- Luciferase reporter assays to determine mRNA stability.
- In vitro studies using hVSMCs cultured in osteogenic media to induce calcification and assess calumenin expression and MGP carboxylation.
Main Results:
- Carriage of the 'G' allele of rs1043550 was associated with lower coronary artery calcium scores.
- Vascular tissues from 'A' allele carriers showed higher calcification, increased calumenin immunostaining, and reduced MGP levels.
- The 'G' allele decreased CALU mRNA stability by 30% in vascular cells.
- Induced hVSMC differentiation showed early calumenin overexpression followed by a decrease, correlating with extracellular matrix mineralization and MGP carboxylation status.
- Calumenin was detected in the mineralized extracellular matrix of calcified arteries.
Conclusions:
- The CALU polymorphism rs1043550 influences calumenin mRNA stability and tissue availability, conferring a protective effect against vascular calcification.
- Calumenin exhibits a dynamic expression pattern during VSMC phenotypic transition and extracellular matrix calcification.
- These findings establish a novel link between VSMC osteogenic transition, calumenin regulation, and vascular calcification.
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