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Soluble levels and endogenous vascular gene expression of KLOTHO are related to inflammation in human atherosclerotic disease.

Authors
  • Martín-Núñez, Ernesto1
  • Donate-Correa, Javier1
  • López-Castillo, Ángel2
  • Delgado-Molinos, Alejandro2
  • Ferri, Carla1
  • Rodríguez-Ramos, Sergio3
  • Cerro, Purificación3
  • Pérez-Delgado, Nayra4
  • Castro, Victoria5
  • Hernández-Carballo, Carolina1
  • Mora-Fernández, Carmen1
  • Navarro-González, Juan F6, 7
  • 1 Research Unit, University Hospital Nuestra Señora de Candelaria, Carretera del Rosario, 145. 38010 Santa Cruz de Tenerife, Spain. , (Spain)
  • 2 Vascular Surgery Service, University Hospital Nuestra Señora de Candelaria, Carretera del Rosario, 145. 38010 Santa Cruz de Tenerife, Spain. , (Spain)
  • 3 Transplantation Coordination, University Hospital Nuestra Señora de Candelaria, Carretera del Rosario, 145. 38010 Santa Cruz de Tenerife, Spain. , (Spain)
  • 4 Clinical Analysis Service, University Hospital Nuestra Señora de Candelaria, Carretera del Rosario, 145. 38010 Santa Cruz de Tenerife, Spain. , (Spain)
  • 5 Pathology Service, University Hospital Nuestra Señora de Candelaria, Carretera del Rosario, 145. 38010 Santa Cruz de Tenerife, Spain. , (Spain)
  • 6 Research Unit, University Hospital Nuestra Señora de Candelaria, Carretera del Rosario, 145. 38010 Santa Cruz de Tenerife, Spain [email protected] , (Spain)
  • 7 Nephrology Service, University Hospital Nuestra Señora de Candelaria, Carretera del Rosario, 145. 38010 Santa Cruz de Tenerife, Spain. , (Spain)
Type
Published Article
Journal
Clinical Science
Publisher
Portland Press
Publication Date
Nov 01, 2017
Volume
131
Issue
21
Pages
2601–2609
Identifiers
DOI: 10.1042/CS20171242
PMID: 28963437
Source
Medline
Keywords
License
Unknown

Abstract

Atherosclerosis is a chronic inflammatory disorder affecting the artery wall. Klotho, an anti-aging factor expressed in the vessel walls that participates in the maintenance of vascular homeostasis, can be down-regulated by inflammation. In this proof-of-concept work we seek to characterize the arterial KLOTHO expression in the vascular wall, as well as the serum concentration of this protein, in a group of patients with clinical atherosclerotic disease. In addition, we aim to analyze the relationship between Klotho and inflammation. Vascular samples were obtained from 27 patients with atherosclerotic disease under an elective vascular surgery procedure, and from 11 control subjects (cadaveric organ donation programme). qRT-PCR was performed to analyze the gene expression of KLOTHO, TNF-α, IL-6, and IL-10 Serum levels of soluble KLOTHO were measured by ELISA. As compared with control subjects, serum concentrations and vascular expression of Klotho were lower in patients with atherosclerotic vascular disease, whereas inflammatory status was significantly higher. There was a negative and significant correlation between inflammatory parameters and Klotho. After controlling for the effect of other variables, partial correlation showed a direct relationship between vascular KLOTHO gene expression and IL-10 mRNA levels, whereas there was a negative association with serum LDL concentrations and vascular TNF-α expression. Our study indicates an inverse interrelationship between inflammation and Klotho in atherosclerosis. Further studies are necessary to elucidate whether the inflammatory state causes Klotho deficiency or, on the contrary, reduction of Klotho could be responsible for greater inflammation, and finally, to investigate the potential clinical relevance of this association.

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