Abstract: TH-OR84
Identification and Characterization of a Vascular Calcification Mediator Originating in the Adrenal Glands
Session Information
- Mechanisms of Hypertension and Cardiorenal Disease: From the Vasculature to the Gut
November 02, 2023 | Location: Room 108, Pennsylvania Convention Center
Abstract Time: 04:57 PM - 05:06 PM
Category: Hypertension and CVD
- 1601 Hypertension and CVD: Basic
Authors
- Bhargava, Shruti, Universitatsklinikum Aachen, Aachen, Nordrhein-Westfalen, Germany
- Wu, Zhuojun, Universitatsklinikum Aachen, Aachen, Nordrhein-Westfalen, Germany
- Jankowski, Vera, Universitatsklinikum Aachen, Aachen, Nordrhein-Westfalen, Germany
- Jankowski, Joachim, Universitatsklinikum Aachen, Aachen, Germany
Background
Patients undergoing dialysis for chronic kidney disease (CKD) foften suffer from vascular calcification, leading to diverse cardiovascular complications. In this study, we conducted a comprehensive investigation to identify and characterize a newly discovered endogenous peptide that plays a regulatory role in vascular calcification processes. Our findings shed light on an unexplored cardioprotective function of the adrenal glands in the context of CKD-associated vascular calcification.
Methods
Chromatographic fractions derived from bovine adrenal glands were tested for their effect on vascular calcification processes using in vitro, ex vivo, and in vivo rat model of elastocalcinosis. To identify potential mediators, mass spectrometric analysis was conducted, and the results were compared with relevant databases.
Results
A 19-aa peptide was discovered and its levels were quantified in the serum of end-stage renal disease patients undergoing dialysis, as well as in matched controls. This newly identified peptide, named Calcification Blocking Factor(CBF), demonstrated significant protective effects against vascular calcification. Treatment with CBF effectively reduced the calcium content in cells, thoracic aortic rings cultured under calcifying conditions, and aortas from elastocalcinosis animal models. CBF exerts its protective effects by inhibiting the transdifferentiation of aortic smooth muscle cells into osteoblast-like cells, which are responsible for driving the progression of vascular calcification. CBF interacts with the sodium-dependent phosphate transporter PIT-1, and hinders NF-κB activation and the BMP2/p-SMAD pathway, all implicated in vascular calcification. CBF treatment reduced arterial stiffness in elastocalcinosis animals. CKD patients, susceptible to vascular calcification, showed decreased CBF concentration in serum.The 19-amino acid peptide is derived from the enzymatic cleavage of the adrenal protein chromograninA by calpain1 and kallikrein. Further analysis revealed that a specific 6-8 amino acid sequence within the 19-amino acid peptide serves as the active site responsible for the calcification-blocking properties of CBF.
Conclusion
Our findings suggest that CBF, a novel inhibitor of vascular calcification derived from the adrenal glands, plays a crucial role in reducing the risk of vascular calcification.
Funding
- Government Support – Non-U.S.