Klotho and SIRT1 changes from pre-diabetes to diabetes and pre-hypertension to hypertension

Abstract

Background Hypertension and diabetes are among the most important risk factors of cardiovascular diseases. Klotho and SIRT1 are known as anti-aging factors with beneficial effects on cardiovascular system. In this study we investigated the serum Klotho and SIRT1 levels in pre-diabetic and pre-hypertensive individuals and then in diabetic and hypertensive patients to see their relationship with these diseases. Method 229 individuals divided into six groups with similar gender and age distribution 1—Control (normal BP and FBS) 2—pre-diabetic (FBS between 100 and 125 mg/dl) 3—diabetic (FBS ≥ 126 mg/dl), 4—pre-hypertensive (SBP 120–139 or DBP 80–89 mm Hg) 5—hypertensive (SBP ≥ 140 or DBP ≥ 90 mm Hg), and 6—patients with combined hypertension/diabetes. Serum levels of Klotho and SIRT1 were measured by ELISA method. Results Serum Klotho and STRT1 levels decreased in pre-diabetes and returned to normal in diabetic patients. Their concentration increased in pre-hypertension and recovered to normal in hypertension. In the physiologic range of FBS there is a negative correlation between Klotho and SIRT1 with FBS. When pathologic ranges of FBS added to analysis, the negative correlation abolished/U shaped. Also an inverse U shape correlation observed between Klotho and SIRT1 with MAP in the range of normal to hypertensive BP levels. There was an overall positive relationship between the serum levels of Klotho and SIRT1 themselves. Conclusion The serum levels of the anti-aging proteins Klotho and SIRT1 increases or reduces at the onset of the disease, as a compensatory mechanism, but as the disease progresses their level recovers.

Association between serum Klotho levels and the prevalence of diabetes among adults in the United States

“…Taken together, the discrepancies among previous publications can be largely attributed to the dynamic changes in Klotho expression at different stages of diabetes. This explanation was consistent with the findings from another study that the serum levels of Klotho increased at the onset of diabetes as a potential compensatory mechanism in response to high glucose stimulation, while their levels recovered as diabetes progressed ( 41 ). More importantly, considering that kidneys act as a major source of endogenous Klotho and the presence of elevated Klotho levels is highly related to preserved renal function ( 42 ), we may speculate that serum Klotho concentration serves as a biomarker of the number of functional nephrons and therefore reflects the degree of renal impairment induced by high glucose.…”

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

“…CEACAM1 [340], ACSL1 [341], TLR4 [342], ABCA1 [343], TLR5 [344], CYP2D6 [345], JAK2 [346], NOTCH2 [347], DDX3X [348], NCOA4 [349], EGR1 [350], IQGAP2 [351], GCLC (glutamate-cysteine ligase catalytic subunit) [352], VEGFA (vascular endothelial growth factor A) [353], ITGB1 [354], LDLR (low density lipoprotein receptor) [355], TLR6 [316], SIRT1 [356], FGL2 [357], TET2 [358], PHF2 [328], VEGFB (vascular endothelial growth factor B) [359], SELENOM (selenoprotein M) [360], TRPM4 [361], OLFM2 [362] and ATAD3A [363] are thought to be involved in non-alcoholic fatty liver disease. Altered expression of ATOH8 [364], STAT1 [365], ARG1 [366], TLR4 [367], VNN1 [368], ABCA1 [369], IFIH1 [370], PTGS2 [371], F2RL1 [289], CYP2D6 [372], PDK4 [373], RNF213 [374], JAK2 [375], NOTCH2 [376], PDGFC (platelet derived growth factor C) [377], TLR2 [378], CYP1B1 [379], IL1RN [380], GCH1 [381], EGR1 [382], HIF1A [383], PLA2G7 [384], CCR2 [385], GAB1 [386], VEGFA (vascular endothelial growth factor A) [387], OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) [388], OXR1 [389], IRF9 [390], FMR1 [391], LDLR (low density lipoprotein receptor) [392], SIRT1 [393], NOD2 [394], ATP13A3 [395], VCAN (versican) [396], FGL2 [397], TET2 [398], KDM6A [399], KLHL2 [400], CAVIN1 [401], TNFRSF4 [402], PF4 [403], VEGFB (vascular endothelial growth factor B) [330], CCR7 [404], PRDX2 [405], HSPB1 [406], TCF4 […”

“…Studies have confirmed that EGR1 [350] and SIRT1 [356] are altered expressed in non-alcoholic fatty liver disease. Previous studies have shown that EGR1 [382], SIRT1 [393], STAT1 [365], HIF1A [383] and IRF9 [390] might influence the prognosis in hypertension. EGR1 [449], SIRT1 [458] and STAT1 [435] are a genes which plays a role in diagnosis of CAD.…”

Expression Landscape and Functional Roles of HOXA4 and HOXA5 in Lung Adenocarcinoma

“…The role of epigenetic regulators in tumor targeted therapy has been of critical interest [30]. The anti-aging gene sirtuin 1 (SIRT1) has been reported to be associated with LUAD and non-small cell lung cancer and high protein level of SIRT1 has been shown to indicate poor prognosis of lung cancer patients [18,[31][32][33]. SIRT1 is involved with transcription dysregulation including deacetylation of transcription factors such as p53 and DNA methylation [34][35][36].…”