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Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
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Aortic microcalcification is associated with elastin fragmentation in Marfan syndrome
Shaynah Wanga1,2,3, Stijntje Hibender1, Yanto Ridwan4
1Department of Medical Biochemistry, Academic Medical Centre Amsterdam, Amsterdam, The Netherlands.
The Journal of Pathology
|July 21, 2017
Summary
Microcalcification in Marfan syndrome (MFS) aortas correlates with elastin degradation. This finding suggests microcalcification can serve as a novel imaging marker to predict aortic events in MFS patients.
Area of Science:
- Cardiovascular Pathology
- Connective Tissue Disorders
- Biomarker Discovery
Background:
- Marfan syndrome (MFS) is a genetic connective tissue disorder.
- Aortic rupture is the primary cause of mortality in MFS patients.
- Current prognostic markers are insufficient for predicting aortic events in MFS.
Purpose of the Study:
- To investigate the role of elastin fragments in aortic calcification in MFS.
- To determine if microcalcification can serve as a prognostic marker for aortic disease severity in MFS.
- To elucidate the molecular mechanisms underlying elastin-induced calcification in MFS aortas.
Main Methods:
- Analysis of MFS patient and mouse aortas for microcalcification and elastic lamina fragmentation.
- In vitro studies using human and murine vascular smooth muscle cells (SMCs) to assess elastin peptide effects on calcification markers.
- Inhibition studies targeting the elastin receptor complex and ERK1/2 signaling pathway.
- In vivo imaging of microcalcification in MFS mouse models using OsteoSense-800.
Main Results:
- MFS patient aortas exhibit enhanced microcalcification associated with elastic lamina fragmentation.
- Elastin peptides increase alkaline phosphatase (ALP) activity and decrease matrix GLA protein in human SMCs.
- Elastin peptide-induced ALP activity in MFS SMCs is mediated by the elastin receptor complex and ERK1/2 activation.
- Microcalcification in MFS mice correlates significantly with aortic diameter, distensibility, elastin breaks, and ERK1/2 phosphorylation.
Conclusions:
- Microcalcification is closely linked to elastin degradation in MFS aortas.
- Elastin-derived peptides promote vascular smooth muscle cell calcification via the elastin receptor and ERK1/2 signaling.
- Microcalcification represents a potential novel imaging biomarker for monitoring aortic disease progression and predicting adverse events in Marfan syndrome.
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