Abstract
Klotho is a soluble or membrane-bound anti-aging protein, whose protective actions are important for a prudential function of many organs. Because Klotho and cerebral small vessel disease (SVD) are associated with ageing process and endothelial dysfunction, it is possible that Klotho has an association with cerebral SVD. We aimed to investigate the association of plasma Klotho concentration with the presence, burden and progression of cerebral SVD. We prospectively enrolled 262 patients with first-ever acute cerebral infarction, performed brain MRI and collected their blood samples within 24 hours of admission. An enzyme-linked immunosorbent assay was used for evaluating plasma Klotho concentration. We estimated the total SVD score of each patient after determining the presence and burden of high-grade white matter hyperintensities (HWMHs), cerebral microbleeds (CMBs), high-grade perivascular spaces (HPVSs) and asymptomatic lacunar infarctions (ALIs). Univariate and multivariate analyses were conducted to investigate association of Klotho with cerebral SVD and the total SVD score. Of the 262 patients, 152 (58.0%) were men. The mean age of these patients was 64.7 years. The mean ± standard deviation of plasma Klotho concentration was 329.8 ± 194.1 pg/mL. In multivariate analysis, plasma Klotho concentration was negatively associated with the presence of HWMHs [Odds ratio (OR): 0.13, p = 0.047], HPVSs (OR: 0.22, p = 0.024) and ALIs (OR: 0.53, p = 0.021) but not associated with the presence of CMBs (OR: 0.39, p = 0.404). Plasma Klotho concentration was also negatively related to the total SVD score (unstandardized coefficients beta: −0.895, standard error = 0.317, p = 0.005, R2 = 0.239). Furthermore, plasma Klotho concentration was negatively related to the presence (OR: 0.75, 95% CI: 0.59–0.96, p = 0.025) and severity of cerebral SVD progression (OR: 0.72, 95% CI: 0.56–0.92, p = 0.009). In conclusion, plasma Klotho concentration was negatively associated with the presence, burden and progression of cerebral SVD.
Highlights
Klotho was a single-pass transmembrane protein encoded by Klotho gene that is predominantly present in the distal tubular cells of the kidney, choroid plexus of the brain and parathyroid glands [1]
The high-grade white matter hyperintensities (HWMHs) were prevalent in 24.4% of subjects (64/ 262); high-grade perivascular spaces (HPVSs), 9.2% (24/262); cerebral microbleeds (CMBs), 19.5% (51/262) and asymptomatic lacunar infarctions (ALIs), 19.5% (51/262)
Plasma Klotho concentration was negatively associated with the presence of HWMHs [Odds ratio (OR): 0.13, 95% confidence interval (CI): 0.01–0.97, p = 0.047)], HPVSs (OR: 0.22, 95% CI: 0.10–0.60, p = 0.024), and ALIs (OR: 0.53, 95% CI: 0.40–0.64, p = 0.021) but not with the presence of CMBs (OR: 0.39, 95% CI: 0.04–3.46, p = 0.404) (Table 3)
Summary
Klotho was a single-pass transmembrane protein encoded by Klotho gene that is predominantly present in the distal tubular cells of the kidney, choroid plexus of the brain and parathyroid glands [1]. The importance of this Klotho has been highlighted in the study involving the Klotho knock-out mouse model, which revealed that Klotho deficiency was related to reduced life expectancy [2] and that Klotho overexpression was associated with life span prolongation [3]. Previous clinical study demonstrated that potential link between klotho deficiency and enhanced oxidative stress in patients with kidney disease [6]
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