Calprotectin is a contributor to and potential therapeutic target for vascular calcification in chronic kidney disease
Ana Amaya-Garrido
(1)
,
Manon Brunet
(1)
,
Bénédicte Buffin-Meyer
(1)
,
Alexis Piedrafita
(1)
,
Lucile Grzesiak
(1)
,
Ezechiel Agbegbo
(1)
,
Arnaud del Bello
(2)
,
Inés Ferrandiz
(2)
,
Serban Ardeleanu
,
Marcelino Bermudez-Lopez
(3)
,
Camille Fedou
(1)
,
Mylène Camus
,
Odile Burlet-Schiltz
(4)
,
Jean Massines
(1)
,
Marie Buléon
(1)
,
Guylène Feuillet
(1)
,
Melinda Alves
(1)
,
Eric Neau
(1)
,
Audrey Casemayou
(1, 2)
,
Benjamin Breuil
(1)
,
Jean-Sébastien Saulnier-Blache
(1)
,
Colette Denis
(1)
,
Jakob Voelkl
,
Griet Glorieux
,
Sam Hobson
,
Samsul Arefin
,
Awahan Rahman
,
Karolina Kublickiene
,
Peter Stenvinkel
,
Jean-Loup Bascands
,
Stanislas Faguer
(1, 2)
,
José Valdivielso
,
Joost Schanstra
(1)
,
Julie Klein
(1)
Ana Amaya-Garrido
- Fonction : Auteur
- PersonId : 1418855
- ORCID : 0009-0008-6037-2638
Bénédicte Buffin-Meyer
- Fonction : Auteur
- PersonId : 870798
- ORCID : 0000-0002-4805-1558
- IdRef : 236206966
Lucile Grzesiak
- Fonction : Auteur
- PersonId : 1418854
- ORCID : 0000-0002-7351-2045
Arnaud del Bello
- Fonction : Auteur
- PersonId : 1131151
- ORCID : 0000-0003-3115-868X
- IdRef : 157884694
Serban Ardeleanu
- Fonction : Auteur
- PersonId : 1432718
- ORCID : 0000-0002-5731-6095
Mylène Camus
- Fonction : Auteur
Odile Burlet-Schiltz
- Fonction : Auteur
- PersonId : 176219
- IdHAL : odile-schiltz
- ORCID : 0000-0002-3606-2356
- IdRef : 155601970
Colette Denis
- Fonction : Auteur
- PersonId : 1282494
- ORCID : 0000-0002-8376-8351
Jakob Voelkl
- Fonction : Auteur
Griet Glorieux
- Fonction : Auteur
- PersonId : 1224163
- ORCID : 0000-0002-7641-4707
Sam Hobson
- Fonction : Auteur
- PersonId : 1354863
- ORCID : 0000-0002-5880-885X
Samsul Arefin
- Fonction : Auteur
- PersonId : 1432719
- ORCID : 0000-0002-8050-9100
Awahan Rahman
- Fonction : Auteur
- PersonId : 1432720
- ORCID : 0000-0002-9504-6065
Karolina Kublickiene
- Fonction : Auteur
- PersonId : 1354866
- ORCID : 0000-0002-4841-6836
Peter Stenvinkel
- Fonction : Auteur
Jean-Loup Bascands
- Fonction : Auteur
- PersonId : 1277859
- ORCID : 0000-0002-1667-5913
Stanislas Faguer
- Fonction : Auteur
- PersonId : 1439834
- ORCID : 0000-0003-0553-0927
- IdRef : 146284135
José Valdivielso
- Fonction : Auteur
- PersonId : 804167
- ORCID : 0000-0003-1343-0184
Joost Schanstra
- Fonction : Auteur
- PersonId : 837350
- ORCID : 0000-0002-7471-372X
- IdRef : 076749304
Julie Klein
- Fonction : Auteur
- PersonId : 901205
- IdHAL : julie-klein-rflab
- ORCID : 0000-0002-3279-0559
Résumé
Vascular calcification is an important risk factor for cardiovascular (CV) mortality in patients with chronic kidney disease (CKD). It is also a complex process involving osteochondrogenic differentiation of vascular smooth muscle cells (VSMCs) and abnormal deposition of minerals in the vascular wall. In an observational, multicenter European study, including 112 patients with CKD from Spain and 171 patients on dialysis from France, we used serum proteome analysis and further validation by ELISA to identify calprotectin, a circulating damage-associated molecular pattern protein, as being independently associated with CV outcome and mortality. This was confirmed in an additional cohort of 170 patients with CKD from Sweden, where increased serum calprotectin concentrations correlated with increased vascular calcification. In primary human VSMCs and mouse aortic rings, calprotectin exacerbated calcification. Treatment with paquinimod, a calprotectin inhibitor, as well as pharmacological inhibition of the receptor for advanced glycation end products and Toll-like receptor 4 inhibited the procalcifying effect of calprotectin. Paquinimod also ameliorated calcification induced by the sera of uremic patients in primary human VSMCs. Treatment with paquinimod prevented vascular calcification in mice with chronic renal failure induced by subtotal nephrectomy and in aged apolipoprotein E–deficient mice as well. These observations identified calprotectin as a key contributor of vascular calcification, and increased circulating calprotectin was strongly and independently associated with calcification, CV outcome, and mortality in patients with CKD. Inhibition of calprotectin might therefore be a promising strategy to prevent vascular calcification in patients with CKD.