Klotho gene expression decreases in peripheral blood mononuclear cells (PBMCs) of patients with relapsing-remitting multiple sclerosis

Karami, Mohammad Reza; Mehrabi, Farzad; Allameh, Abdolamir; Kakhki, Majid Pahlevan; Amiri, Mehdi; Aleagha, Mohammad Sajad Emami

doi:10.1016/j.jns.2017.09.012

Cited by 17 publications

(6 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, we observed similar associations between KL, DNMT1 and DNMT3A expression in PBCCs and parameters of systemic in ammation (serum concentrations of TNFα, IL10 and their ratio). Other studies have appreciated associations between the development of several diseases characterized by a pro-in ammatory pro le and the reduction of KL gene expression in these cells 38,40,57 . Observations in the present study support these previous ndings and also suggest that the pro-in ammatory systemic state, either evidenced in PBCCs or in serum cytokines concentrations, could regulate KL expression in leukocytes by activation of the methylation process.…”

Section: Discussionmentioning

confidence: 99%

Klotho expression in peripheral blood circulating cells is associated with vascular and systemic inflammation in atherosclerotic vascular disease

Martín‐Núñez

Pérez-Castro

Ferri

et al. 2022

Preprint

View full text Add to dashboard Cite

Cardiovascular disease (CVD) is the leading cause of death worldwide. New therapeutic strategies are aimed to modulate the athero-inflammatory process that partially orchestrates underlying vascular damage. Peripheral blood circulating cells (PBCCs) include different immune cells with a central role in the development of the atherogenic inflammatory response. The anti-aging factor α-Klotho (KL) has been related to protective effects against CVD. KL is expressed in monocytes, macrophages and lymphocytes where it exerts anti-inflammatory effects. Our aim is to characterize the relationships between inflammatory markers and KL gene expression in PBCCs or serum levels of soluble KL (sKL) in atherosclerotic vascular disease. For this, we conducted a cross-sectional single center case-control study including 76 CVD patients and a control group of 16 cadaveric organ donors without medical antecedent or study indicating CVD. Vascular artery fragments, whole blood and serum samples were obtained during elective or organ retrieval surgery, respectively. Serum levels of sKL, TNFα and IL10 were measured. Gene expression levels of KL, TNF, IL10, NFKB1, DNMT1, and DNMT3A, and KL promoter methylation percentage in PBCCs were also determined. Histological and immunohistochemical analyses were employed to visualize atherosclerotic lesions and to measure IL10 and TNFα levels in vascular fragments.CVD patients presented higher values for pro-inflammatory markers in the vasculature, PBCCs and systemically compared to controls. In PBCCs, CVD group presented lower expression of KL gene compared to controls (56.4% reduction, P<0.001), which was accompanied by higher methylation of its promoter (34.1±4.1% vs. 14.6±3.4%, P<0.01) and higher gene expression of DNMT1 and DNMT3A (P<0.0001 for both). KL expression correlated inversely with pro-inflammatory markers in PBCCs and vasculature, but directly with anti-inflammatory markers. sKL serum levels presented similar associations with pro- and anti-inflammatory markers in PBCCs. KL expression in PBCCs and serum sKL levels were diminished in patients with macroscopically observable atheromatous plaques.We conclude that KL gene downregulation in PBCCs during atherosclerotic vascular disease, which is mediated by promoter methylation, is associated with the pro-inflammatory status developed in this disorder either in the vasculature or systemically.

show abstract

Section: Discussionmentioning

confidence: 99%

Klotho expression in peripheral blood circulating cells is associated with vascular and systemic inflammation in atherosclerotic vascular disease

Martín‐Núñez

Pérez-Castro

Ferri

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…VNN1 is the critical molecule that modulates the dependent reaction of glutathione to oxidative damage in epithelial cells. Relevant studies have testified that urinary VNN1 distinctly ascends in patients with nephropathy, implying that urinary VNN1 is able to be employed as a biomarker of renal tubular injury [ 9 , 10 ]. Presently, the role of SIRT6 in a variety of diseases is yet disputable, and some scholars maintain that it is a tumor suppressor modulating the occurrence and advancement of multiple tumor diseases [ 11 , 12 ].…”

Section: Discussionmentioning

confidence: 99%

Aberrant Expression of SIRT6 and VNN1 in Peripheral Blood Monocytes of Children with Primary Nephrotic Syndrome and Its Diagnostic and Prognostic Values

Han

Yuan

et al. 2022

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Objective. The objective is to explore the aberrant sirtuin-6 (SIRT6) and Vanin-1 (VNN1) protein expression in peripheral blood monocytes (PBM) of children with primary nephrotic syndrome (PNS) and its diagnostic and prognostic values. Methods. 83 child patients with nephrotic syndrome (NS) and 65 healthy volunteers were enrolled in the study. The test of SIRT6 and VNN1 was performed by the Western blot. The receiver operator characteristic (ROC) curve was used to analyze the diagnostic and prognostic value of SIRT6 and VNN1 for child patients with NS. The logistic regression was used to analyze the association of SIRT6 and VNN1 with the prognosis of NS child patients. Results. SIRT6 in monocytes in the study group was inferior versus the control, while VNN1 outweighed it. The AUC of the combined detection of SIRT6 and VNN1 for the diagnosis of NS was 0.854, with a sensitivity of 80.0% and a specificity of 80.7%. The AUC of combined detection of SIRT6 and VNN1 for the prognosis of NS was 0.860, with a sensitivity of 84.6% and a specificity of 79.2%. The logistic regression analysis showed that less than 21.09 in SIRT6 was the number of risk factors for the prognosis of NS child patients ( P < 0.05 ). Conclusion. SIRT6 and VNN1 are provided with diagnostic and prognostic values for NS.

show abstract

“…42,43 . Klotho has been previously detected in PBCs and marked reductions in Klotho expression in PBCs has been related with aging and with the development of pathologies with an inflammatory component including atherosclerosis 41,44,45 www.nature.com/scientificreports/ of Klotho in these cells could be beneficial in antagonizing the progression of atherosclerotic lesions through antiinflammatory effects. In this sense, the expression of Klotho in these cells has been related with the attenuation of lipopolysaccharide (LPS)-induced acute inflammation in macrophages and with the inactivation of NF-kB signaling and the promotion of M2 polarization in these cells, which infiltrates atheromatous plaques and develop a defensive and repair response to vascular damage 46,47 .…”

Section: Discussionmentioning

confidence: 99%

Klotho as a biomarker of subclinical atherosclerosis in patients with moderate to severe chronic kidney disease

Donate‐Correa

Ferri

Martín‐Núñez

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Chronic kidney disease (CKD) has been associated with a higher risk of cardiovascular disease (CVD). CKD patients present a decrease in the levels of the protein Klotho that accompanies the decrease in kidney function. This protein has been related to protective effects against CVD. However, it is unclear whether circulating Klotho, and its expression in peripheral blood cells (PBCs) are also associated with subclinical atherosclerosis in CKD. The present study aimed to study the relationship between Klotho and subclinical atherosclerosis in a population of patients with moderate to severe CKD. We determined the serum levels and gene expression in PBCs levels of Klotho and three inflammatory cytokines in 103 patients with CKD and investigated their relationship with two surrogate markers of subclinical atherosclerotis: ankle-brachial index (ABI) and carotid intima-media thickness (CIMT). Patients with subclinical atherosclerosis presented lower serum and PBCs expression levels of Klotho. Both variables were associated with the presence of subclinical atherosclerosis, being directly related with ABI and inversely with CIMT (P < 0.0001 for both). Multiple regression analysis demonstrated that both variables were significant determinants for ABI (adjusted R2 = 0.511, P < 0.0001) and CIMT (adjusted R2 = 0.445, P < 0.0001), independently of traditional and emergent cardiovascular risk factors. Moreover, both constituted protective factors against subclinical atherosclerosis [OR: 0.993 (P = 0.002) and 0.231 (P = 0.025), respectively]. Receiver operating characteristic analysis pointed to the utility of serum Klotho (area under the curve [AUC]: 0.817, 95% CI: 0.736–0.898, P < 0.001) and its gene expression in PBCs (AUC: 0.742, 95% CI: 0.647–0.836, P < 0.001) to distinguish subclinical atherosclerosis. The reductions in serum and PBCs expression levels of Klotho in CKD patients are independently associated with the presence of for subclinical atherosclerosis. Further research exploring whether therapeutic approaches to maintain or elevate Klotho could reduce the impact of CVD in CKD patients is warranted.

show abstract

Klotho gene expression decreases in peripheral blood mononuclear cells (PBMCs) of patients with relapsing-remitting multiple sclerosis

Cited by 17 publications

References 14 publications

Klotho expression in peripheral blood circulating cells is associated with vascular and systemic inflammation in atherosclerotic vascular disease

Klotho expression in peripheral blood circulating cells is associated with vascular and systemic inflammation in atherosclerotic vascular disease

Aberrant Expression of SIRT6 and VNN1 in Peripheral Blood Monocytes of Children with Primary Nephrotic Syndrome and Its Diagnostic and Prognostic Values

Klotho as a biomarker of subclinical atherosclerosis in patients with moderate to severe chronic kidney disease

Contact Info

Product

Resources

About