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Isolation and Characterization of Primary Rat Valve Interstitial Cells: A New Model to Study Aortic Valve Calcification
Published on: November 20, 2017
Human aortic valve calcification is associated with an osteoblast phenotype
Nalini M Rajamannan1, Malayannan Subramaniam, David Rickard
1Division of Cardiology, Northwestern University Feinberg School of Medicine, Northwestern University, 201 East Huron St, Galter Suite 10-240, Chicago, Ill 60611, USA. n.rajamannan@northwestern.edu
Circulation
|April 30, 2003
Summary
Aortic valve calcification, a common cardiovascular disease, involves an active, regulated process similar to bone formation. This process is linked to an osteoblast-like phenotype, suggesting a regulated mechanism rather than random degeneration.
Area of Science:
- Cardiovascular Biology
- Bone Metabolism
- Biomineralization
Background:
- Calcific aortic stenosis is a prevalent cardiovascular disease.
- The underlying mechanism of aortic valve calcification remains incompletely understood.
- A hypothesis suggests similarity to skeletal bone formation mediated by osteoblast-like cells.
Purpose of the Study:
- To investigate the mechanism of aortic valve calcification.
- To determine if aortic valve calcification involves an osteoblast-like phenotype.
- To compare gene and protein expression in calcified versus normal human aortic valves.
Main Methods:
- Analysis of human aortic valves (n=22 calcified, n=20 normal) using microradiography and micro-CT.
- Histological staining (von Kossa, Goldner's) to identify mineralization.
- Electron microscopy and energy-dispersive spectroscopy for ultrastructure and elemental analysis.
- Reverse transcriptase-polymerase chain reaction (RT-PCR) for osteoblast markers (osteopontin, bone sialoprotein, osteocalcin, alkaline phosphatase, Cbfa1).
Main Results:
- Microradiography and micro-CT confirmed valve calcification.
- Histological stains and electron microscopy identified hydroxyapatite and CaPO4 composition.
- RT-PCR showed increased mRNA levels for osteopontin, bone sialoprotein, osteocalcin, and Cbfa1 in calcified valves.
- Alkaline phosphatase showed increased protein expression, but not mRNA, in diseased valves.
Conclusions:
- Aortic valve calcification is an active, regulated process.
- The process is associated with an osteoblast-like cellular phenotype.
- Findings support a bone-formation-like mechanism in aortic valve calcification.
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