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.
Highlights
Klotho (KL) is a longevity-related gene discovered in 1997 [1]
The clinical diagnosis consisted of peripheral artery disease (PAD) (66.4%), transient ischemic attack (TIA) (39.1%), and abdominal aortic aneurysm (AAA) (18.2%)
The analysis revealed that soluble Klotho levels were significantly associated with age, estimated glomerular filtration rate (eGFR), serum levels of C-reactive protein (CRP) and IL10, and with the TNFα/IL10 ratio
Summary
Klotho (KL) is a longevity-related gene discovered in 1997 [1]. Defects in KL expression leads to a syndrome resembling human aging that includes endothelial dysfunction, vascular calcification and progressive atherosclerosis [1]. Several clinical studies have observed that lower systemic levels of the soluble form of Klotho are associated with markers of vascular dysfunction [7,8,9,10] as well as with the prevalence and severity of cardiovascular disease (CVD) [11,12,13]. These associations are relevant in renal patients since the largest proportion of systemic Klotho is generated by the kidneys and its levels are reduced along with the renal function decline [14]
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