Research Paper Volume 11, Issue 15 pp 5445—5462
Impact of C-reactive protein on osteo-/chondrogenic transdifferentiation and calcification of vascular smooth muscle cells
- 1 Department of Internal Medicine and Cardiology, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin 13353, Germany
- 2 Institute for Physiology and Pathophysiology, Johannes Kepler University Linz, Linz 4040, Austria
- 3 Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
- 4 Department of Endocrinology, Diabetes and Nutrition, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin 10115, Germany
- 5 DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin 10115, Germany
- 6 Department of Physiology I, Eberhard-Karls University, Tübingen 72076, Germany
- 7 Berlin Institute of Health (BIH), Berlin 10178, Germany
- 8 Department of Internal Medicine and Cardiology, German Heart Center Berlin (DHZB), Berlin 13353, Germany
- 9 Calciscon AG, 2560 Nidau-Biel, Switzerland
- 10 Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin 10117, Germany
Received: February 28, 2019 Accepted: July 25, 2019 Published: August 3, 2019https://doi.org/10.18632/aging.102130
How to Cite
Copyright © 2019 Henze et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Medial vascular calcification occurs during the aging process and is strongly accelerated by chronic kidney disease (CKD). Elevated C-reactive protein (CRP) levels are associated with vascular calcification, cardiovascular events and mortality in CKD patients. CRP is an important promoter of vascular inflammation. Inflammatory processes are critically involved in initiation and progression of vascular calcification. Thus, the present study explored a possible impact of CRP on vascular calcification. We found that CRP promoted osteo-/chondrogenic transdifferentiation and aggravated phosphate-induced osteo-/chondrogenic transdifferentiation and calcification of primary human aortic smooth muscle cells (HAoSMCs). These effects were paralleled by increased cellular oxidative stress and corresponding pro-calcific downstream-signaling. Antioxidants or p38 MAPK inhibition suppressed CRP-induced osteo-/chondrogenic signaling and mineralization. Furthermore, silencing of Fc fragment of IgG receptor IIa (FCGR2A) blunted the pro-calcific effects of CRP. Vascular CRP expression was increased in the klotho-hypomorphic mouse model of aging as well as in HAoSMCs during calcifying conditions. In conclusion, CRP augments osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells through mechanisms involving FCGR2A-dependent induction of oxidative stress. Thus, systemic inflammation may actively contribute to the progression of vascular calcification.