1. ETS-Related Gene Expression in Healthy Femoral Arteries With Focal Calcifications
- Author
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Gianandrea Pasquinelli, Alessio Degiovanni, Carmen Ciavarella, Sabrina Valente, Francesco Vasuri, Ilenia Motta, Vasuri F., Valente S., Motta I., Degiovanni A., Ciavarella C., and Pasquinelli G.
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,QH301-705.5 ,Context (language use) ,Femoral artery ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Cell and Developmental Biology ,0302 clinical medicine ,medicine.artery ,EndMT ,elastic lamina ,Medicine ,Biology (General) ,Original Research ,biology ,business.industry ,CD44 ,arterial calcification ,Cell Biology ,medicine.disease ,femoral artery ,Arterial calcification ,030104 developmental biology ,ERG ,Osteocalcin ,biology.protein ,Immunohistochemistry ,business ,Erg ,Developmental Biology ,Calcification - Abstract
Bone development-related genes are enriched in healthy femoral arteries, which are more prone to calcification, as documented by the predominance of fibrocalcific plaques at the femoral location. We undertook a prospective histological study on the presence of calcifications in normal femoral arteries collected from donors. Since endothelial-to-mesenchymal transition (EndMT) participates in vascular remodeling, immunohistochemical (IHC) and molecular markers of EndMT and chondro-osteogenic differentiation were assessed. Transmission electron microscopy (TEM) was used to describe calcification at its inception. Two hundred and fourteen femoral arteries were enrolled. The mean age of the donors was 39.9 ± 12.9 years; male gender prevailed (M: 128). Histology showed a normal architecture; calcifications were found in 52 (24.3%) cases, without correlations with cardiovascular risk factors. Calcifications were seen on or just beneath the inner elastic lamina (IEL). At IHC, SLUG was increasingly expressed in the wall of focally calcified femoral arteries (FCFA). ETS-related gene (ERG), SLUG, CD44, and SOX-9 were positive in calcifications. RT-PCR showed increased levels of BPM-2, RUNX-2, alkaline phosphatase, and osteocalcin osteogenic transcripts and increased expression of the chondrogenic marker, SOX-9, in FCFA. TEM documented osteoblast-like cells adjacent to the IEL, releasing calcifying vesicles from the cell membrane. The vesicles were embedded in a proteoglycan-rich matrix and were entrapped in IEL fenestrations. In this study, ERG- and CD44-positive cell populations were found in the context of increased SLUG expression, thus supporting the participation of EndMT in FCFA; the increased transcript expression of osteochondrogenic markers, particularly SOX-9, reinforced the view that EndMT, osteochondrogenesis, and neoangiogenesis interact in the process of arterial calcification. Given its role as a transcription factor in the regulation of endothelial homeostasis, arterial ERG expression can be a clue of endothelial dysregulation and changes in IEL organization which can ultimately hinder calcifying vesicle diffusion through the IEL fenestrae. These results may have a broader implication for understanding arterial calcification within a disease context.
- Published
- 2021