Serum fetuin-A Research Articles

Clinical significances of circulating serum fetuin-A, netrin-1, and ɑ-hydroxybutyrate levels in type 2 diabetes mellitus patients with and without hypertension

Background & Objective: Type 2 diabetes (T2D) is a rising global health issue, with biomarkers such as fetuin-A (Fet-A), netrin-1 (NTN-1), and alpha-hydroxybutyrate (α-HB) showing potential for early diagnosis and management. These biomarkers can help predict T2D risk and understand insulin resistance (IR), emphasizing the need for further research. The current investigation evaluated the effectiveness of Fet-A, NTN-1, and, α-HB as novel biomarkers to diagnose T2D with hypertension. Methodology: A cross-sectional study was conducted from August to December 2023, involved 60 diabetic participants, which were divided into two groups: T2D without hypertension and T2D with hypertension. A third group consisted of 30 healthy controls (HC) for comparison. Serum samples were analyzed for fasting blood glucose (FBG) using the Roche/Cobas c111 system, as well as insulin, Fet-A, NTN-1, and α-HB levels using kits for the enzyme-linked immune-sorbent assay (ELISA). Descriptive statistics were used in the statistical package for social sciences (SPSS) for data analysis. Results: The study found significantly elevated Fet-A, NTN-1, and α-HB levels in T2D patients compared to HC, with no significant differences between T2D subgroups. Fetuin-A and α-HB showed non-significant correlations with FBG and homeostatic model assessment of IR (HOMA-IR) across all groups. NTN-1 positively correlated with FBG and HOMA-IR in T2D patients with hypertension. Conclusions: Elevated levels of fetuin-A and netrin-1, regardless of the presence of hypertension, are suggested by the study as possible biomarkers for the diagnosis of T2D. Netrin-1's significant correlation with HOMA-IR in hypertensive T2D patients underscores its utility in assessing insulin resistance severity. Although alpha-hydroxybutyrate levels were higher in T2D patients, their non-significant correlation with FBG and HOMA-IR requires further research. These biomarkers could aid in early diagnosis and disease monitoring for T2D management. Abbreviations: α-KB - α-ketobutyrate; ELISA - enzyme linked immune-sorbent assay; FA - fatty acids; FBG - fasting blood glucose; Fet-A - fetuin-A; HOMA-IR - homeostatic model assessment of IR; IR - insulin resistance; NAD - nicotinamide adenine dinucleotide; NADH - nicotinamide adenine dinucleotide hydrogen; ng - nanograms; NTN-1 - netrin-1; PB - peripheral blood; pg - picogram; SPSS - Statistical Package for Social Sciences; T2D - Type-2 diabetes mellitus; α-HB - alpha-hydroxybutyrate Keywords: Diabetes, Fetuin-A, Netrin-1, α-HB, HOMA-IR. Citation: Sfayyih HS, Jewad AM, Khudhair HAA. Clinical significance of circulating serum fetuin-A, netrin-1, and ɑ-hydroxybutyrate levels in type-2 diabetes mellitus patients with and without hypertension. Anaesth. pain intensive care 2024;28(5):883−893; DOI: 10.35975/apic.v28i5.2569 Received: Jul 22, 2024; Reviewed: August 10, 2024; Accepted: August 15, 2024

Association of Serum Fetuin-A and Fatty Liver Index as an Indicator of Hepatic Steatosis in Chronic HCV Patients

Association of Serum Fetuin-A and Fatty Liver Index as an Indicator of Hepatic Steatosis in Chronic HCV Patients

#372 Cross-sectional association between serum magnesium with cognition in patients undergoing hemodialysis: the Osaka Dialysis Complication Study

Abstract Background and Aims Impaired cognitive performance is common in patients with chronic kidney disease including those undergoing haemodialysis, although the mechanisms are not well understood by which chronic kidney disease affects cognitive function. Phosphate plays an important role in the development of aging phenotypes particularly in patients with chronic kidney disease. Phosphate toxicity is thought to be mediated by calciprotein particles, and a shorter T50 reflects a higher propensity of transformation of primary to secondary calciprotein particles. T50 is known to be affected by phosphate, fetuin-A, magnesium, and others. We examined possible relationship between cognitive function and CKD-MBD-related factors in patients undergoing haemodialysis. Method This was a cross-sectional study in 1207 patients on maintenance haemodialysis selected from the participants of Osaka Dialysis Complication Study (ODCS). Cognitive function was assessed by Modified Mini-Mental State examination (3MS). Associations of serum calcium, phosphate, intact PTH, magnesium, fetuin-A, and T50 with 3MS was examined by multiple regression models adjusted for age, sex, dialysis vintage, diabetic kidney disease, prior stroke, prior non-stroke cardiovascular disease, education level, SBP, DBP, Hb, BMI, serum albumin, and CRP. Results Serum magnesium and phosphate levels were significantly and positively associated with 3MS level independent of the potential confounders, whereas other factors were not. Conclusion We found positive associations of cognitive performance with serum magnesium and phosphate levels in haemodialysis patients, suggesting the roles of CKD-MBD-related factors in impaired cognition in this population.

Effect of rosuvastatin on sortilin and fetuin-A in type 2 diabetic patients: a randomized controlled trial

Abstract Objective Rosuvastatin is a drug used for decreasing the risk of cardiovascular complications in type 2 diabetes mellitus (T2DM) patients. It is hypothesized that fetuin-A encourages lipid-induced insulin resistance and sortilin may increase the risk of atherosclerotic-related disorders. The aim of this study is to investigate the safety and efficacy of rosuvastatin co-treatment in T2DM patients and its effect on levels of sortilin and fetuin-A. Methods Seventy T2DM patients treated with glimepiride and metformin were randomly assigned to either co-treated with rosuvastatin 10 mg tablets (rosuvastatin group, n = 40), or placebo (placebo group, n = 30) daily for 3 months in a parallel, double-blind randomized controlled trial. Blood was collected for biochemical analysis. Serum sortilin and fetuin-A levels, glycemic and lipid profiles were measured before and 3 months after intervention. Results Fasting blood glucose (FBG, mg/dl) significantly decreased in placebo and rousvastatin groups from (104 ± 7.24 to 96.67 ± 7.14 vs 102.8 ± 6.43 to 93.0 ± 4.71), respectively, compared with baseline (p < 0.05). BMI and HbA1c decreased in placebo vs rosuvastatin group (29.20 ± 3.18 to 28.10 ± 3.08, p=0.08 vs 28.67 ± 3.56 to 27.66 ± 3.16, p = 0.27), and (6.59 ± 0.27 to 6.36 ± 0.27 vs 6.56 ± 0.26 to 6.29 ± 0.25), respectively, compared with baseline (p ≤ 0.001) with no significance difference between both groups (p = 0.58 and p = 0.25, respectively). Sortilin and fetuin-A levels significantly decreased in rosuvastatin vs placebo group from (1.77 ± 0.41 to 0.64 ± 0.37 vs 1.70 ± 0.36 to 1.65 ± 0.36) and from (295.33 ± 52.04 to 179.75 ± 60.22 vs 307.22 ± 50.11 to 288.94 ± 49.53), respectively, compared with baseline with significance difference between both groups (p < 0.001) compared with placebo. Significant positive correlation was found between sortilin with fetuin-A, low-density lipoprotein (LDL-C), and atherogenic index (p < 0.001). Significant positive correlation was observed between fetuin-A with FBG (p < 0.05) and atherogenic index (p < 0.001). Conclusion Rosuvastatin co-treatment in T2DM patients improves glycemic control and aids in decreasing the atherogenic biomarkers sortilin and fetuin-A levels, so it can be considered tolerable and efficient in improving lipid profile and atherogenic index. Trial registration ClinicalTrials.gov identifier (NCT number): NCT03907423, (The registration date: April 9, 2019). https://clinicaltrials.gov/ct2/show/NCT03907423.

Serum fetuin-a and risk of thoracic aortic aneurysms: a two-sample mendelian randomization study.

Recent studies have revealed a significant decrease in serum fetuin-A levels in atherosclerotic aneurysms, indicating that fetuin-A may play a protective role in the progression of arterial calcification. However, the specific mechanism behind this phenomenon remains unclear. We aimed to examine the association between fetuin-A levels in thoracic aortic aneurysms (TAAs) and risk of TAAs and to evaluate whether this association was causal. A total of 26 SNPs were selected as instrumental variables for fetuin-A in 9,055 participants of European ancestry from the CHARGE consortium, and their effects on thoracic aortic aneurysm and decreased descending thoracic aortic diameter were separately estimated in 353,049 and 39,688 individuals from FinnGen consortium. We used two-sample Mendelian randomization (MR) analysis to examine the causal association. At the same time, we employed various methods, including random-effects inverse variance weighting, weighted median, MR Egger regression, and MR PRESSO, to ensure the robustness of causal effects. We assessed heterogeneity using Cochran's Q value and examined horizontal pleiotropy through MR Egger regression and retention analysis. Fetuin-A level was associated with a significantly decreasing risk of thoracic aortic aneurysm (odds ratio (OR) 0.64, 95% CI 0.47 - 0.87, P = 0.0044). Genetically predicted fetuin-A was also correlated with the decreased descending thoracic aortic diameter (β = -0.086, standard error (SE) 0.036, P = 0.017). Serum fetuin-A level was negatively associated with risk of TTAs and correlated with the decreased descending thoracic aortic diameter. Mendelian randomization provides support for the potential causal relationship between fetuin-A and thoracic aortic aneurysm.

Clinical and Biochemical Parameters in Relation to Serum Fetuin-A Levels in Overweight and Obese with and without Metabolic Syndrome in the North-eastern States of Indian Population

Clinical and Biochemical Parameters in Relation to Serum Fetuin-A Levels in Overweight and Obese with and without Metabolic Syndrome in the North-eastern States of Indian Population

Pigment epithelium-derived factor (PEDF) represses the glucose transporter 1 (GLUT1) mRNA expression and may be a potential therapeutic agent in psoriasis: a case–control and experimental study

We investigated the whole blood GLUT1 mRNA expression and serum pigment epithelium-derived factor (PEDF), interleukin-6 (IL-6), fetuin-A, and pentraxin-3 (PTX3) levels in psoriatic patients and tested their correlations with the severity of psoriasis using the psoriasis area and severity index (PASI) score. Also, we tested the GLUT1 mRNA expression after an in vitro treatment of human skin fibroblast (HSF) cell lines with PEDF. The case–control part of the study recruited 74 participants (44 psoriatic patients and 30 healthy volunteers). Whole blood GLUT1 mRNA fold changes were estimated by RT-PCR, and serum PEDF, IL-6, fetuin-A, and PTX3 levels were measured by ELISA kits. In the experimental part, the HSF cell lines were treated with different concentrations of PEDF for different times to test its effect on the GLUT1 mRNA expression. The whole blood GLUT 1 expression significantly increased in psoriatic patients and correlated positively with serum IL-6, fetuin-A, PTX3 levels and with the severity of psoriasis while negatively with serum PEDF levels. The PEDF-treated HSF cell lines showed a time- and dose-dependent decline in the GLUT 1 mRNA expression. The whole blood GLUT 1 mRNA is a non-invasive biomarker that is associated with the severity of psoriasis. PEDF represses GLUT 1 expression and may be a potential therapeutic agent in psoriasis.Trial registration: ClinicalTrials.gov Identifier: NCT04242082.

Evaluation of Serum Fetuin-A as A Possible Marker for Polycystic Ovarian Syndrome Among Iraqi Women; Case-control Study

Elevated levels of Fetuin-A, a protease inhibitor belonging to the cystatin family, have raised questions about its role in the pathogenesis of Polycystic Ovarian Syndrome (PCOS), the most prevalent endocrinopathy in reproductive-aged females. This case-control study, conducted in Iraq, aimed to assess changes in Fetuin-A levels among Iraqi women with PCOS. A convenient sample of 90 women, comprising 45 PCOS cases and 45 healthy controls, was enrolled. Fetuin-A levels were measured and found to be significantly higher in the PCOS group compared to controls. Additionally, significant positive correlations were observed between Fetuin-A levels and fasting plasma glucose, fasting serum insulin, insulin resistance, luteinizing hormone, and serum testosterone. Using a receiver operating characteristic curve, a cutoff point of 502.00 ng/mL was determined for predicting positive Fetuin-A levels, with a sensitivity and specificity of 84.4% and 73.3%, respectively. This study suggests that Fetuin-A could serve as a valuable marker for both screening and evaluating PCOS and its potential late consequences, including metabolic syndrome.
 Highlights:
 
 
 Elevated Fetuin-A Levels: This study reveals significantly higher Fetuin-A levels in PCOS, shedding light on its potential role in the pathogenesis of the syndrome.
 
 
 Correlations with Metabolic Factors: Positive correlations between Fetuin-A and key metabolic markers like fasting glucose, insulin resistance, and luteinizing hormone highlight its relevance in the context of PCOS and metabolic health.
 
 
 Screening Potential: The identified cutoff point for predicting positive Fetuin-A levels offers a promising tool for screening and evaluating PCOS and associated late consequences, particularly metabolic syndrome.
 

Serum fetuin-A in diabetic and nondiabetic hemodialysis patients

Serum fetuin-A in diabetic and nondiabetic hemodialysis patients

Enhancement of protein immobilization on polydimethylsiloxane using a synergistic combination of polydopamine and micropattern surface modification

Understanding protein interactions at biointerfaces is critical for the improved design of biomaterials and medical devices. Polydimethylsiloxane (PDMS) is used for numerous device applications, and surface modifications can enhance protein immobilization and the response to cells. A multifunctional approach combining topographical and biochemical modifications was applied to PDMS by fabricating 10–20 µm scale patterns onto PDMS surfaces and by coating with polydopamine (PDA). The modifications were confirmed by surface characterization and bovine serum albumin (BSA), fibrinogen (Fg), and fetuin-A (Fet-A) were radiolabeled with 125I. The amounts of protein attached to the surface before and after elution with sodium dodecyl sulfate (SDS) were quantified from single and complex multi-protein solutions to determine protein stability and competitive binding. The PDA coatings were the most stable and capable of immobilizing the highest levels of all proteins. Furthermore, combinations of PDA coatings with the smallest micropatterns provided an additional improvement, enhancing the amount immobilized and the stability. The adsorption of BSA and Fg from plasma demonstrated competitive binding and possible orientation changes, respectively. It was determined that Fet-A, a less studied protein, adsorbed from plasma at low levels, but the adsorption from fetal bovine serum (FBS) was significantly greater, providing important quantification data from radiolabeling that is relevant to many cell culture studies. Overall, combining topography and PDA modification has a synergistic effect on improving protein immobilization. These findings provide new insight on the quantities of proteins bound to PDMS and PDA coatings with implications for cell interactions in various biotechnology and medical applications.

Effect of Fetuin-A and oxidative stress on the occurrence of unexplained infertility.

Unexplained infertility refers to a diagnosis in which all standard examinations are usually normal and is statistically seen in approximately 30-40% of infertile couples and endometriosis encountered in 25-50% of patients with unexplained infertility. Unexplained infertility is thought to be closely associated with endometriosis and serum and peritoneal fluid levels of Fetuin-A is increased in patients with endometriosis. Fetuin-A is proposed as a diagnostic marker for endometriosis and has anti-inflammatory effects on several diseases. Oxidative stress also is central to the etiopathogenesis of infertility in women. The aim of this study was to evaluate serum Fetuin-A and oxidative stress parameter concentrations impact on unexplained infertility. In the study, serum Fetuin-A, IL-1β, CA I, TAS, TOS levels, and PON and ARE enzyme activities were measured using the Enzyme-Linked ImmunoSorbent Assay in the sera of diagnosed unexplained infertility females (n=44) and controls (n=41). There was no statistically significant difference between unexplained infertile patients and control groups in terms of serum IL-1β, CA I, OSI, and PON levels (p>0.05). Serum Fetuin-A and ARE levels were significantly higher in unexplained infertility compared with the control, whereas serum TAS and TOS levels were lower (p<0.05, p<0.01, p<0.05, p<0.05, respectively). It is thought that increased Fetuin-A levels may be a response to the inflammatory process and increased ARE activity may be a sign of the impaired oxidant-antioxidant balance in unexplained infertility. This may contribute to the pathogenesis of infertility, and the data obtained will make a significant contribution to new works to be done in this sense.

The usability of MCP-1, fetuin-A, TAS, and TOS levels in the diagnosis of acute myocardial infarction.

Our aims were to determine whether the levels of plasma monocyte chemotactic protein-1 (MCP-1), fetuin-A, serum total antioxidant status (TAS), and serum total oxidant status (TOS) are cardiac biomarkers and to clarify their relationship with each other in acute myocardial infarction (AMI). The study included 90 participants: 60 patients with AMI [30 with and 30 without ST-segment elevation myocardial infarction (STEMI)] and 30 cardiac patients without AMI. The diagnostic values of serum Hs-cTnT, MCP-1, fetuin-A, TAS, and TOS levels in predicting AMI were evaluated statistically. Median levels of MCP-1 [120.10 ng/L (interquartile range: 76.94-230.54 ng/L)] and TOS [2.89 U/MI (IQR: 2.31-3.94 U/Ml)] were statistically higher, and median levels of fetuin-A [433.52 mg/L (IQR: 387.89-584.49 mg/L)] and TAS (3.10 ± 0.86 U/mL) were lower in patients with AMI than in controls. The parameter with the area under the curve (0.815), sensitivity (73.3%), and specificity (66.7%) closest to those of Hs-cTnT was fetuin-A, followed by MCP-1, TOS, and TAS, respectively. A one-unit increase in MCP-1 levels increased the probability of AMI by 1.023 times (p = 0.002). A one-unit increase in fetuin-A levels decreased the probability of AMI by 0.995 times (p = 0.003). A one-unit increase in serum TOS levels was 1.29 times more characteristic of STEMI than of NSTEMI (p = 0.044). MCP-1, oxidative stress parameters, and fetuin-A might support Hs-cTnT levels in the early diagnosis of AMI. Fetuin-A and MCP-1 levels may be independent risk factors for AMI, whereas TOS could be used to distinguish STEMI from NSTEMI.

Can Fetuin-A Deficiency Predict the Severity of COVID-19 Disease in Kidney Transplant Recipients?

BackgroundThis study aims to investigate whether fetuin A deficiency predicts the prognosis of COVID-19 disease in kidney transplant recipients (KTRs). MethodThe study was conducted on 35 hospitalized KTRs with COVID-19 pneumonia between November 2020 and June 2021. Serums were collected for fetuin-A measurement at admission and after six months of follow-up. The demographic and laboratory data of the patients were recorded and analyzed with the appropriate statistical method. ResultsA total of 35 KTRs, 23 of which (65.7%) were men, were included in the study. The mean age of the patients was 51.6 ± 14.0 years. Seventeen (48.6%) patients had severe disease criteria and required intensive care (ICU) support. Biopsy-proven acute rejection developed in 6 (17.1%) patients in the follow-up. At admission, the median fetuin-A value was 173.5 mcg/mL (143.5-199.25) in the moderate disease group and 126.0 mcg/mL (89.4-165.5) in the severe patient group (p = 0.005). While the Median fetuin-A value at the time of diagnosis was 173.5 mcg/mL (143.5-199.25), and in the 6th month was 208 mcg/mL [184-229] (p<0.001). By ROC analysis, the effect of serum fetuin-A level in predicting the severity of COVID-19 disease was significant (AUC: 0.771, p = 0.006, 95% CI: 0.615-0.927). When serum fetuin-A cut-off value was taken as 138 mcg/mL to determine disease severity, it was shown to have 83.3% sensitivity and 64.7% specificity. ConclusionsSerum fetuin-A level can predict disease severity in kidney transplant recipients in the presence of active COVID-19 disease.

Serum fetuin-A is decreased in cirrhotic patients with Wilson's disease.

Wilson's disease may lead to cirrhosis, but timely medical treatment could slow down its progression. Clinical markers helping early diagnosis are essential. Decreased fetuin-A concentration has been reported in cirrhosis of different etiologies. The aim of this study was to investigate whether decreased serum fetuin-A concentration could identify patients with Wilson's disease who developed cirrhosis. In this cross-sectional study we determined the serum fetuin-A concentration of 50 patients with Wilson's disease. We analyzed the data of patients with liver involvement, comparing cirrhotic and non-cirrhotic patients. Among patients with liver involvement those with cirrhosis had significantly lower fetuin-A and albumin level, white blood cell and platelet count. Fetuin-A negatively correlated with disease duration, bilirubin level, positively with total protein and albumin concentration, but not with copper and ceruloplasmin concentrations or markers of systemic inflammation. In multivariate analysis with fetuin-A and the Nazer score or its parameters only fetuin-A was a significant determinant of having cirrhosis. In receiver operator curve analysis among patients with liver involvement the fetuin-A level of 523 μg/ml was associated with cirrhosis with 82% sensitivity and 87% specificity. The presence of the H1069Q mutation was not associated with alteration in fetuin-A concentration. The serum concentration of fetuin-A is a sensitive marker of liver cirrhosis in Wilson's disease, independently of the H1069Q mutation, ceruloplasmin concentration or systemic inflammation.

Can Serum Fetuin-A be Used as a Marker for Cardiovascular Involvement in Psoriatic Patients?

Psoriasis is a systemic inflammatory disorder. It is associated with increased risk of developing other chronic health diseases such cardiovascular disorders. Fetuin A is a glycoprotein that is present in blood serum. It may prevent vascular calcification by forming calciprotien particles; which are formed from their attachment with phosphate and calcium complexes. The aim of this study was to measure serum Fetuin A in Psoriatic patients and correlate its level with cardiac events and risks in these patients using CT calcium (Ca) scoring. 24 psoriatic patients (healthy without apparent cardiac risks to detect subclinical events if present) and 24 age and sex matched controls were tested for serum Fetuin A and underwent coronary calcium scoring by multidetector computed tomography (CT) scan. Psoriasis area and severity index (PASI) score for each patient was measured and was correlated with serum Fetuin A and CT calcium (Ca) scoring. Serum Fetuin A was compared between cases and controls and was correlated with coronary calcium score. There was highly statistically significant decrease in serum Fetuin A level in psoriatic group compared to control group (P-value < .001). There was highly statistically significant negative correlation between calcium score and the level of serum Fetuin A (P-value < .001). No statistically significant correlation was found between the serum level of Fetuin A and the psoriasis severity. Serum Fetuin A is a simple, easy diagnostic tool to evaluate subclinical atherosclerosis in psoriatic patients.

Assessment of serum fetuin-A and its gene polymorphism as a marker of insulin resistance in polycystic ovary syndrome

Background/aim Polycystic ovary syndrome (PCOS) is a prevalent endocrine condition affecting 5–10% of reproductive-aged women, the cause of which is unknown. Chronic anovulation, polycystic ovaries, and hyperandrogenism are symptoms of PCOS. It is linked to hirsutism, obesity, and increased probability of cardiovascular disease, metabolic syndrome, and diabetes mellitus. A risk factor for cardiovascular disease is PCOS that is undiagnosed or untreated. Our aim in this study is to investigate serum fetuin-A level and its gene as potential biomarkers for screening of insulin resistance in PCOS. Patients and methods This study involved 100 female participants from outpatient clinic, Department of Obstetrics and Gynecology, Zagazig University Hospital, Egypt. They were split into two groups (each 50). The first group included healthy fertile women without symptoms of hyperandrogenemia as a control. The second group included women with PCOS. Fasting blood sugar levels, cholesterol, high-density lipoprotein cholesterol and triglycerides have been estimated by enzymatic colorimetric technique while low-density lipoprotein cholesterol was calculated. Enzyme-linked immunosorbent assays have been used to measure serum concentrations of luteinizing hormone, follicular-stimulating hormone, testosterone, and fetuin-A, while PCR has been used to extract DNA and genotype common functional polymorphisms in fetuin-A. Results The present results revealed a considerable rise in glucose, insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), cholesterol, triglyceride, low-density lipoprotein cholesterol, luteinizing hormone, testosterone, and fetuin-A and significant decrease in follicular-stimulating hormone and high-density lipoprotein cholesterol in PCOS patients. Also, there was significant higher frequency of the fetuin-A gene variant rs1071592 AA genotype and A allele compared to controls. Conclusions Fetuin-A has a potential diagnostic value as a biomarker for insulin resistance in PCOS associated with metabolic syndrome. Additionally, ‘CG’ allele can be considered a risk factor for PCOS.

Can Bone-Specific Alkaline Phosphatase be a Marker of Vascular Calcification in Type 2 Diabetes Mellitus?

Alkaline phosphatase (ALP) enzyme has been linked to vascular calcification. Unexplained elevations in serum ALP levels have been reported in patients with type 2 diabetes mellitus (T2DM). We assessed bone-specific alkaline phosphatase (BAP) levels in patients with T2DM who had unexplained ALP elevations and studied the association between BAP and other markers of vascular calcification. Patients with T2DM who had high serum ALP in the absence of known causes of ALP elevation were studied. The control group was T2DM patients with normal ALP. We measured the serum levels of BAP along with the leptin, fetuin-A, and vitamin K2 levels. Ankle-brachial index (ABI) was also measured in both groups. Serum BAP levels were significantly higher in the group with high ALP when compared with the normal ALP group. A significant positive correlation was present between BAP and serum fetuin-A as well as between BAP and Vit K2 levels. There was no correlation between BAP and serum leptin. ABI was comparable between the two groups. Patients with T2DM may have unexplained elevation in ALP due to an increase in BAP. Elevation in BAP may be associated with other markers of vascular calcification suggesting an increased risk of vascular calcification.

Humoral and cellular factors inhibit phosphate-induced vascular calcification during the growth period.

Hyperphosphatemia is an independent and non-classical risk factor of cardiovascular disease and mortality in patients with chronic kidney disease (CKD). Increased levels of extracellular inorganic phosphate (Pi) are known to directly induce vascular calcification, but the detailed underlying mechanism has not been clarified. Although serum Pi levels during the growth period are as high as those observed in hyperphosphatemia in adult CKD, vascular calcification does not usually occur during growth. Here, we have examined whether the defence system against Pi-induced vascular calcification can exist during the growth period using mice model. We found that calcification propensity of young serum (aged 3 weeks) was significantly lower than that of adult serum (10 months), possibly due to high fetuin-A levels. In addition, when the aorta was cultured in high Pi medium in vitro, obvious calcification was observed in the adult aorta but not in the young aorta. Furthermore, culture in high Pi medium increased the mRNA level of tissue-nonspecific alkaline phosphatase (TNAP), which degrades pyrophosphate, only in the adult aorta. Collectively, our findings indicate that the aorta in growing mouse may be resistant to Pi-induced vascular calcification via a mechanism in which high serum fetuin-A levels and suppressed TNAP expression.

Ethyl palmitate ameliorates lethal endotoxemia by inducing hepatic fetuin-A secretion: an in vivo and in vitro experiment.

Ethyl palmitate (EP) is known to promote hepatic fetuin-A production and modulate inflammatory responses, but its potential role in lethal endotoxemia and sepsis remains unclear. This study investigates the plasma fetuin-A levels and further evaluates the impact of hepatic fetuin-A induced by EP on systemic inflammation and macrophage polarization in lethal endotoxemia and sepsis. Blood samples from 55 sepsis patients and 18 non-septic controls with similar age and sex ratio were collected to perform proteomic analyses and identify significantly different proteins. Serum fetuin-A levels in lipopolysaccharide (LPS) induced endotoxemia mice were assayed by enzyme-linked immunosorbent assay (ELISA). The mouse hepatocyte cell (AML-12) was exposed to different concentrations of EP. In vivo experiments were conducted in which adult male C57BL/6J mice were given EP with or without intraperitoneal LPS. Fetuin-A was determined via western blot and immunohistochemical staining. Survival rates, lung and liver injury and levels of pro-inflammatory cytokines were also monitored and assessed using histology, real-time quantitative polymerase chain reaction (RT-qPCR) and ELISA. Additionally, the proportion of macrophages and M1/M2 subtypes in the lung and liver tissues were evaluated by flow cytometry. Our proteomic results revealed that the plasma fetuin-A levels were significantly decreased in sepsis patients compared with non-septic controls. Similarly, the serum fetuin-A levels were also reduced in endotoxemia mice compared with the control group. EP effectively promoted the production of fetuin-A in AML-12 cells and murine liver tissues. Subsequently, activation of fetuin-A by EP dramatically reduced LPS-induced murine mortality, alleviated lung and liver injury, down-regulated pro-inflammatory mediators and macrophage infiltration. Furthermore, EP regulated macrophage polarization from the M1 (CD45+CD11b+F4/80+CD86+) to the M2 (CD45+CD11b+F4/80+CD206+) subtype in murine liver tissue. EP-induced production of fetuin-A prevents sepsis and endotoxemia progression by promoting M2 polarization of macrophages.

Serum fetuin-A as a perdictive biomarker of chronic kidney disease

Serum fetuin-A as a perdictive biomarker of chronic kidney disease