Prevention of vascular calcification by the endogenous chromogranin A-derived mediator that inhibits osteogenic transdifferentiation

Autor: Walter Zidek, Danilo Fliser, Àngel Argilés, Heike Bruck, Christoph Kuppe, Heidi Noels, Setareh Orth-Alampour, Nikolaus Marx, Vera Jankowski, Shruti Bhargava, Nathalie Gayrard, Joseph Loscalzo, Zhuojun Wu, Cécile Notarnicola, Bernard Jover, Emiel P. C. van der Vorst, Silvia Salem, Michael Wolf, Wendy Theelen, Claudia Goettsch, Joachim Jankowski
Přispěvatelé: RWTH Aachen University, Université de Montpellier (UM), RD-Néphrologie (R&D), Hannover Medical School [Hannover] (MHH), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), III. Medical Clinic, University Medical Center Mannheim, Medizinische Klinik IV, Charité Campus Benjamin Franklin, Harvard Medical School [Boston] (HMS), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Maastricht University [Maastricht], Biocommunication en Cardio-Métabolique (BC2M), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Pathologie, RS: Carim - B07 The vulnerable plaque: makers and markers
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Vascular smooth muscle
Physiology
SMOOTH-MUSCLE-CELLS
Cell
Mesenchymal cell differentiation
Medizin
030204 cardiovascular system & hematology
Muscle
Smooth
Vascular
VIVO
CALCIUM DEPOSITION
0302 clinical medicine
RAT MODEL
Cells
Cultured
0303 health sciences
biology
Chemistry
Transdifferentiation
Chromogranin A
Calpain
Original Contribution
3. Good health
medicine.anatomical_structure
SECRETORY VESICLES
cardiovascular system
Cardiology and Cardiovascular Medicine
ARTERIAL STIFFNESS
EXPRESSION
medicine.medical_specialty
PHOSPHATE-INDUCED CALCIFICATION
OSTEOBLASTIC DIFFERENTIATION
Cardiorenal syndrome
Myocytes
Smooth Muscle
Context (language use)
Adrenal glands
03 medical and health sciences
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Physiology (medical)
Internal medicine
medicine
Animals
Humans
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
Vascular smooth muscle cell transdifferentiation
Vascular Calcification
030304 developmental biology
Vascular smooth muscle cell transdiferentiation
IN-VITRO
medicine.disease
Endocrinology
Cell Transdifferentiation
biology.protein
Vascular calcifcation
Calcification
Zdroj: Basic Research in Cardiology
Basic Research in Cardiology, Springer Verlag, 2021, 116 (1), pp.57. ⟨10.1007/s00395-021-00899-z⟩
Basic Research in Cardiology, 116(1):57. Springer
ISSN: 0300-8428
1435-1803
Popis: 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. Supplementary Information The online version contains supplementary material available at 10.1007/s00395-021-00899-z.
Databáze: OpenAIRE
Externí odkaz: