Prevention of vascular calcification by the endogenous chromogranin A-derived mediator that inhibits osteogenic transdifferentiation.
Adrenal glands
Cardiorenal syndrome
Vascular calcification
Vascular smooth muscle cell transdifferentiation
Journal
Basic research in cardiology
ISSN: 1435-1803
Titre abrégé: Basic Res Cardiol
Pays: Germany
ID NLM: 0360342
Informations de publication
Date de publication:
13 10 2021
13 10 2021
Historique:
received:
05
05
2021
accepted:
01
10
2021
revised:
15
09
2021
entrez:
14
10
2021
pubmed:
15
10
2021
medline:
14
1
2022
Statut:
epublish
Résumé
The adrenal glands participate in cardiovascular (CV) physiology and the pathophysiology of CV diseases through their effects on sodium and water metabolism, vascular tone and cardiac function. In the present study, we identified a new adrenal compound controlling mesenchymal cell differentiation that regulates osteoblastic differentiation in the context of vascular calcification. This peptide was named the "calcification blocking factor" (CBF) due to its protective effect against vascular calcification and is released from chromogranin A via enzymatic cleavage by calpain 1 and kallikrein. CBF reduced the calcium content of cells and thoracic aortic rings under calcifying culture conditions, as well as in aortas from animals treated with vitamin D and nicotine (VDN animals). Furthermore, CBF prevented vascular smooth muscle cell (VSMC) transdifferentiation into osteoblast-like cells within the vascular wall via the sodium-dependent phosphate transporter PIT-1 and by inhibition of NF-κB activation and the subsequent BMP2/p-SMAD pathway. Pulse pressure, a marker of arterial stiffness, was significantly decreased in VDN animals treated with CBF. In line with our preclinical data, CBF concentration is significantly reduced in diseases characterized by increased calcification, as shown in patients with chronic kidney disease. In preparation for clinical translation, the active site of the native 19-AS long native CBF was identified as EGQEEEED. In conclusion, we have identified the new peptide CBF, which is secreted from the adrenal glands and might prevent vascular calcification by inhibition of osteogenic transdifferentiation. The anti-calcific effects of CBF and short active site may therefore promote the development of new tools for the prevention and/or treatment of vascular calcification.
Identifiants
pubmed: 34647168
doi: 10.1007/s00395-021-00899-z
pii: 10.1007/s00395-021-00899-z
pmc: PMC8514386
doi:
Substances chimiques
Chromogranin A
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
57Informations de copyright
© 2021. The Author(s).
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