title: Targeting local vascular and systemic consequences of inflammation on vascular and cardiac valve calcification.
abstract: BACKGROUND
  Cardiac valve calcification and vascular calcification (VC) are associated with cardiovascular mortality in the general population and in patients with chronic kidney disease (CKD). CKD, diabetes mellitus, and atherosclerosis are among the causes of systemic inflammation that are associated with VC.
  
  
  METHODS
  This review collates clinical and experimental evidence that inflammation accelerates VC progression. Specifically, we review the actions of key pro-inflammatory cytokines and inflammation-related transcription factors on VC, and the role played by senescence. Inflammatory cytokines, such as the TNF superfamily and IL-6 superfamily, and inflammation-related transcription factor NF-κB promote calcification in cultured vascular smooth muscle cells, valvular interstitial cells, or experimental animal models through direct effects, but also indirectly by decreasing circulating Fetuin A or Klotho levels.
  
  
  CONCLUSIONS
  Experimental evidence suggests a causal link between inflammation and VC that would change the clinical approach to prevention and treatment of VC. However, the molecular basis remains unclear and little is known about VC in humans treated with drugs targeting inflammatory cytokines. The effect of biologicals targeting TNF-α, RANKL, IL-6, and other inflammatory mediators on VC, in addition to the impact of dietary phosphate in patients with chronic systemic inflammation, requires study.
authors.affiliation: a 1 Universidad Autónoma de Madrid, School of Medicine, Nephrology, IIS-Fundación Jiménez Díaz , Madrid, Spain.
authors.forename: Lucie
authors.initials: L
authors.lastname: Hénaut
authors.affiliation: b 2Universidad Autónoma de Madrid, School of Medicine, IIS-Fundación Jiménez Díaz, Madrid, Spain.|c 3 REDINREN , Madrid, Spain.
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Sanchez-Nino
authors.affiliation: d 4 Universidad Autónoma de Madrid, School of Medicine, IIS-Fundación Jiménez Díaz , Madrid, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Aldamiz-Echevarría Castillo
authors.affiliation: b 2Universidad Autónoma de Madrid, School of Medicine, IIS-Fundación Jiménez Díaz, Madrid, Spain.|c 3 REDINREN , Madrid, Spain.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Sanz
authors.affiliation: c 3 REDINREN , Madrid, Spain.|e 5 Chief of nephrology, Universidad Autónoma de Madrid, School of Medicine, IIS-Fundación Jiménez Díaz , Madrid, Spain aortiz@fjd.es.|f 6 Fundación Renal Iñigo Alvarez de Toledo-IRSIN , Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
mesh_terms: D000818:Animals; D002114:Calcinosis / Q000473:pathology / Q000628:therapy; D002318:Cardiovascular Diseases / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D006349:Heart Valve Diseases / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000473:pathology*; D058990:Molecular Targeted Therapy; D061205:Vascular Calcification / Q000473:pathology* / Q000628:therapy
chemical_list: D016207:Cytokines
keywords: aging; aortic stenosis; chronic kidney disease; inflammation; senescence; vascular calcification; vascular cell