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Updated: Oct 17, 2025
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Prevention of vascular calcification by the endogenous chromogranin A-derived mediator that inhibits osteogenic
Setareh Orth-Alampour1, Nathalie Gayrard2, Silvia Salem3
1Institute of Molecular Cardiovascular Research, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
Abstract:
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.
Insights
Researchers discovered a new adrenal peptide, calcification blocking factor (CBF), that prevents vascular calcification by inhibiting osteogenic transdifferentiation. This peptide holds potential for developing new treatments for vascular calcification.
Area of Science:
- Endocrinology and Metabolism
- Cardiovascular Physiology
- Vascular Biology
Background:
- Adrenal glands influence cardiovascular physiology and disease pathophysiology.
- Vascular calcification is a pathological process involving mesenchymal cell differentiation.
- Osteoblastic differentiation contributes to vascular calcification.
Purpose of the Study:
- To identify and characterize a novel adrenal compound involved in regulating vascular calcification.
- To investigate the mechanism by which this compound prevents osteoblastic differentiation in vascular cells.
- To evaluate the therapeutic potential of this compound for vascular calcification.
Main Methods:
- Identification of a new peptide, calcification blocking factor (CBF), from chromogranin A.
- Enzymatic cleavage by calpain 1 and kallikrein to release CBF.
- In vitro and in vivo experiments using cell cultures and animal models (VDN animals).
- Assessment of calcium content, cell differentiation markers, and arterial stiffness (pulse pressure).
- Analysis of signaling pathways including PIT-1, NF-κB, and BMP2/p-SMAD.
- Measurement of CBF levels in patients with chronic kidney disease.
Main Results:
- CBF significantly reduced calcium content in cells and aortic rings.
- CBF prevented vascular smooth muscle cell transdifferentiation into osteoblast-like cells.
- CBF inhibited vascular calcification via the PIT-1 transporter and NF-κB/BMP2/p-SMAD pathway.
- Pulse pressure was significantly decreased in VDN animals treated with CBF.
- CBF levels were reduced in patients with chronic kidney disease, correlating with calcification.
Conclusions:
- A novel adrenal peptide, CBF, has been identified with potent anti-calcific properties.
- CBF prevents vascular calcification by inhibiting osteogenic transdifferentiation of vascular cells.
- The active site of CBF (EGQEEEED) offers potential for therapeutic development.
- CBF represents a promising target for novel treatments against vascular calcification.
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