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Research Paper|Volume 12, Issue 2|pp 1952—1964

Association between serum levels of Klotho and inflammatory cytokines in cardiovascular disease: a case-control study

Ernesto Martín-Núñez1,2, Javier Donate-Correa1, Carla Ferri1,2, Ángel López-Castillo3, Alejandro Delgado-Molinos3, Carolina Hernández-Carballo1,2, Nayra Pérez-Delgado4, Sergio Rodríguez-Ramos5, Purificación Cerro-López5, Víctor G. Tagua1, Carmen Mora-Fernández1, Juan F. Navarro-González1,6,7
  • 1Research Unit, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
  • 2Doctoral and Graduate School, University of La Laguna, San Cristóbal de La Laguna, Spain
  • 3Vascular Surgery Service, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
  • 4Clinical Analysis Service, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
  • 5Transplant Coordination, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
  • 6Nephrology Service, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
  • 7Institute of Biomedical Technologies, University of La Laguna, San Cristóbal de La Laguna, Spain
* Equal contribution
Received: November 5, 2019Accepted: January 2, 2020Published: January 27, 2020
https://doi.org/10.18632/aging.102734

Copyright: © 2020 Martín-Núñez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Decrease in soluble anti-aging Klotho protein levels is associated to cardiovascular disease (CVD). Diverse studies have shown a bidirectional relationship between Klotho and inflammation, a risk factor for the development of CVD. In this work we aimed to evaluate the association between Klotho and inflammatory cytokines levels in the context of human CVD.

The study included 110 patients with established CVD and preserved renal function, and a control group of 22 individuals without previous history of cardiovascular events. Serum Klotho and IL10 levels were significantly lower in the CVD group. Inflammatory status, marked by the TNFα/IL10 ratio and the C-reactive protein (CRP) levels, was significantly increased in the group of patients with established CVD. Soluble Klotho levels were directly correlated with eGFR (r=0.217) and IL10 (r=0.209) and inversely correlated with age (r=-0.261), CRP (r=-0.203), and TNFα/IL10 (r=-0.219). This association with TNFα/IL10 remained significant in age-matched subgroups. Multiple logistic regression analysis showed that age, smoking and the neutrophil-to-lymphocyte ratio (NLR) constituted risk factors for the presence of CVD, while Klotho was a protective factor.

In conclusion, in patients with established CVD, the reduction in soluble Klotho is associated with a pro-inflammatory status marked by lower IL10 concentrations and higher TNFα/IL10 ratio and CRP levels.