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Low Serum Level of Klotho Is an Early Predictor of Atherosclerosis
Nursen Keles1, Mustafa Caliskan, Burcu Dogan
1Department of Cardiology, Goztepe Training and Research Hospital, Istanbul Medeniyet University.
Insights
Low serum Klotho levels are linked to early signs of atherosclerosis, including increased epicardial fat thickness and carotid intima-media thickness, and decreased flow-mediated dilation in healthy adults.
Area of Science:
- Cardiovascular Research
- Endocrinology
- Aging Biology
Background:
- The Klotho gene encodes a transmembrane protein with a soluble form acting as a potential vasculoprotective hormone.
- Epicardial fat thickness (EFT), carotid intima-media thickness (CIMT), and flow-mediated dilation (FMD) are established early predictors of atherosclerosis.
- Investigating novel biomarkers for early atherosclerosis detection is crucial for preventative cardiovascular strategies.
Purpose of the Study:
- To examine the association between serum Klotho levels and established early atherosclerotic markers (EFT, CIMT, FMD) in a healthy adult population.
- To determine if serum Klotho levels can serve as a predictor of subclinical atherosclerosis.
- To explore the role of Klotho in vascular health and aging.
Main Methods:
- Serum Klotho levels were quantified using the ELISA method in 50 healthy volunteers.
- Participants were stratified into higher Klotho (HK) and lower Klotho (LK) groups based on median serum levels.
- EFT, CIMT, and FMD were measured using transthoracic echocardiography and standard vascular assessment techniques.
Main Results:
- The lower Klotho (LK) group exhibited significantly reduced FMD (p = 0.012) compared to the HK group.
- The LK group demonstrated significantly increased EFT (p = 0.01) and CIMT (p < 0.001) compared to the HK group.
- Low serum Klotho levels were significantly associated with markers of increased atherosclerosis risk.
Conclusions:
- Reduced serum Klotho levels are correlated with adverse cardiovascular risk markers, including increased EFT and CIMT, and decreased FMD.
- Serum Klotho may represent a novel, independent predictor of early atherosclerosis in healthy individuals.
- These findings highlight the potential role of Klotho in vascular homeostasis and atherosclerosis development.
Abstract:
The Klotho gene, identified as an 'aging suppressor' gene, encodes a single-pass transmembrane protein. The extracellular domain of Klotho is cleaved and released in the blood stream, where it may function as a vasculoprotective hormone. Carotid artery intima-media thickness (CIMT), flow-mediated dilation (FMD) of the brachial artery and epicardial fat thickness (EFT) have been reported as early predictors of atherosclerosis. We aimed to investigate the relationship between serum Klotho levels and early atherosclerotic predictors, including EFT, FMD and CIMT in healthy adults. Fifty healthy volunteers were enrolled in this study, consisting of 21 males and 29 females with median age of 32 years. They were free of known risk factors for cardiovascular diseases. Serum Klotho levels were determined by the ELISA method. The study population was divided into two groups (n = 25 for each) according to the median serum Klotho level (459.4 pg/mL): higher Klotho (HK) group (613.6 pg/mL; ranges of 501.2-772.6 pg/mL) and lower Klotho (LK) group (338.7 pg/mL; ranges of 278.8-430.3 pg/mL). EFT was measured by transthoracic echocardiography, and CIMT and FMD were measured with standard procedures. The LK group showed lower values of FMD (p = 0.012) and larger values of EFT (p = 0.01) and CIMT (p < 0.001), compared to the HK group. Thus, the low serum Klotho levels were associated with increased EFT and CIMT and with the decreased FMD in the study population. We propose that the lower serum Klotho level is a newly identified predictor of atherosclerosis.
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