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Endochondral bone formation in the heart: a possible mechanism of coronary calcification
L A Fitzpatrick1, R T Turner, E R Ritman
1Department of Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. fitz@mayo.edu
Insights
Atherosclerotic calcification in rat hearts resembles bone formation. This suggests endochondral ossification may drive vascular calcification, a regulated process, not passive mineral precipitation.
Area of Science:
- Cardiovascular Biology
- Skeletal Biology
- Biomineralization
Background:
- Atherosclerotic calcification is linked to adverse cardiovascular events.
- Previously viewed as passive, vascular calcification is now understood as a regulated process.
- Bone mineralization involves endochondral ossification, where cartilage is remodeled into bone.
Purpose of the Study:
- To investigate the mechanism of calcification in aged rat hearts.
- To determine if vascular calcification follows pathways similar to bone formation.
Main Methods:
- Histological analysis of aged female Sprague Dawley rat hearts.
- Micro-computerized tomography radiogrammetry for quantitative imaging.
- Immunohistochemical staining for cartilage and bone markers.
Main Results:
- Presence of cartilage and chondrocytes confirmed in rat heart tissue.
- Micro-CT imaging validated calcified tissue architecture.
- Staining revealed markers for cartilage (Type II, X, procollagen I) and bone (osteocalcin, osteopontin, etc.).
Conclusions:
- Aged rat hearts exhibit cartilage, indicative of endochondral ossification.
- Proteins typical of bone calcification are present in vascular cartilage.
- Endochondral ossification is a potential mechanism for vascular calcification in atherosclerosis.
Abstract:
During the atherosclerotic process, calcification occurs and is associated with a high likelihood of adverse events. Coronary calcification has been perceived as a passive precipitation of mineral. Recently, calcification associated with atherosclerosis has been found to be the result of an organized, regulated process that is similar to the process of calcification in bone. Mineralization in skeletal tissue can form by endochondral ossification in which mesenchymal cells differentiate into chondroblasts and produce a cartilage matrix which then degenerates and is remodeled to form bone. In this study, hearts from oophorectomized, aged female Sprague Dawley rats were found to contain areas of cartilage. Micro-computerized tomography radiogrammetry provided quantitative images of the architecture and confirmed the calcified tissue. Histological analysis revealed staining for several markers consistent with cartilage and bone tissue: acid phosphatase and bone matrix proteins, osteocalcin, osteopontin, osteonectin, and bone sialoprotein. In addition, cartilage types II, X, and procollagen type I were present. The presence of chondrocytes in the aged rat heart provides insights into the process of calcification in coronary arteries. Many proteins associated with calcification in bone are present in the cartilage that is present in vascular tissue, suggesting that endochondral calcification is another possible mechanism by which calcification of vascular tissue may occur.