Low Serum Level of Klotho Is an Early Predictor of Atherosclerosis

Low Serum Level of Klotho Is an Early Predictor of Atherosclerosis

NURSEN KELES,¹ MUSTAFA CALISKAN,¹ BURCU DOGAN,² NECIBE NUR KELES,³ MACIT KALCIK,⁴ FEYZA AKSU,¹ OSMAN KOSTEK,⁵ SOE MOE AUNG,⁶ BANU ISBILEN⁷ and AYTEKIN OGUZ⁵

¹Department of Cardiology, Goztepe Training and Research Hospital, Istanbul Medeniyet University, Istanbul, Turkey
²Department of Family Physicians, Goztepe Training and Research Hospital, Istanbul Medeniyet University, Istanbul, Turkey
³Eyup Government Hospital Neurology Clinics, Istanbul, Turkey
⁴Department of Cardiology, Iskilip Atif Hoca State Hospital, Corum, Turkey
⁵Department of Internal Medicine, Goztepe Training and Research Hospital, Istanbul Medeniyet University, Istanbul, Turkey
⁶Department of Cardiology, Fatih University, Istanbul, Turkey
⁷Department of Biochemistry, Goztepe Training and Research Hospital, Istanbul Medeniyet University, Istanbul, Turkey

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.

keywords —— atherosclerosis; carotid artery intima-media thickness; epicardial fat thickness; flow-mediated dilation; Klotho

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Tohoku J. Exp. Med., 2015, 237, 17-23

Correspondence: Nursen Keles, M.D., Department of Cardiology, Goztepe Training and Research Hospital, Istanbul Medeniyet University, Doktor Erkin Caddesi, Kadiköy, Istanbul, Turkey.

e-mail: drnursenkeles@yahoo.com.tr