Sfrp5 Levels Research Articles

Prognostic significance of serum secreted frizzled-related protein 5 in patients with acute aortic dissection

BackgroundSecreted frizzled-related protein 5 (SFRP5) is a novel adipokine that has been found to be closely associated with metabolic and cardiovascular diseases. We investigated serum SFRP5 levels during the acute phase and their predictive value for the prognosis of acute aortic dissection (AAD). MethodsIn total, 152 AAD patients and 164 controls were enrolled in this study. Serum SFRP5 levels were measured using an enzyme-linked immunosorbent assay (ELISA). AAD patients were divided into high-SFRP5 and low-SFRP5 groups based on the optimal cutoff value and followed up for prognosis. The primary endpoint was all-cause mortality, and the secondary endpoint focused on AAD-related events (including AAD-related mortality and unplanned reoperations). ResultsSerum SFRP5 levels were significantly higher in AAD patients than in non-AAD controls, regardless of whether they had Stanford type A or B AD. Multivariate logistic regression analysis revealed an independent association between SFRP5 and the presence of AAD (adjusted OR 1.267, 95 % CI 1.152–1.394; p < 0.001). The receiver operating characteristic curve demonstrated that the optimal cutoff value for SFRP5 to predict the presence of AAD was 10.26 ng/mL (AUC 0.7241, sensitivity 49.34 %, specificity 87.20 %). Notably, serum SFRP5 levels of patients in the death group were significantly higher than those in the survival group. Compared with patients in the low-SFRP5 group, those in the high-SFRP5 group exhibited a significantly increased risk of all-cause mortality (HR 9.540, 95 % CI 2.803–32.473; p < 0.001) and AAD-related events (HR 6.915, 95 % CI 2.361–20.254; p < 0.001) during the follow-up period. ConclusionSerum SFRP5 levels were significantly elevated in the acute phase of AAD, and high serum SFRP5 levels were independently associated with poor AAD prognosis. These results suggest that serum SFRP5 level during the acute phase may be an effective biomarker and therapeutic target for the prognosis of AAD.

Expression of secreted frizzled-related proteins in acute aortic dissection patients and the effects on prognosis.

Secreted frizzled-related proteins (SFRPs) were reported to be involved in cardiovascular diseases. This study aimed to observe plasma SFRP levels in acute aortic dissection (AD) patients and the effects of SFRP expression on AD prognosis. Plasma levels of SFRP1, SFRP2, SFRP3, SFRP4, and SFRP5 were measured in AD patients and non-AD (NAD) patients. The end-point events information of AD patients, including all-cause death and various clinical complications due to aortic dissection, was collected during a 36-month follow-up. The SFRP1, SFRP2, SFRP3, and SFRP4 levels were increased in AD patients compared with those in NAD patients, while the SFRP5 concentrations were decreased. No differences in any of the SFRP levels were observed between the type A group and the type B group. The AD patients with end-point events exhibited higher SFRP1, SFRP2, SFRP3, and SFRP4 concentrations but lower SFRP5 levels than the patients without end-point events. In addition, the AD patients were divided into a high group and a low group based on the median SFRP levels, and Kaplan-Meier analysis revealed that the AD patients with high SFRP1, SFRP2, SFRP4, or SFRP5 levels had a better prognosis than those with low levels. However, the AD patients with high SFRP3 levels exhibited the opposite trends. The binary logistic regression analysis found that SFRP1, SFRP2, SFRP4, and SFRP5 were all negatively correlated with the occurrence of end-point events, while SFRP3 was positively correlated with its occurrence. SFRP levels are all changed in acute AD, which may affect the prognosis of AD patients. SFRPs may be a target to improve the prognosis of AD.

The synergy of serum SFRP5 levels and the TyG index in predicting coronary artery disease and prognosing major adverse cardiovascular events.

Secreted frizzled-related protein 5 (SFRP5) is a member of the SFRP family that is known for its potent anti-inflammatory properties. Nevertheless, little is known regarding the relevance of SFRP5 in coronary artery disease (CAD). The current study examined the correlation between serum levels of SFRP5 and the triglyceride-glucose (TyG) index in patients who underwent coronary angiography (CAG) as a component of cardiovascular assessment and for the purpose of prognosis evaluation. A total of 310 hospitalized patients were enrolled in this study between May 2021 and March 2022 and were divided into three groups based on their CAG results and SYNTAX (synergy between PCI with TAXUS drug-eluting stent and cardiac surgery) scores: the control group, mild lesion group, and moderate-severe lesion group. Univariate and multivariate analyses were employed to investigate the relationships between changes in patients and clinical variables. To investigate the impact of the TyG index and serum SFRP5 levels on the occurrence of major adverse cardiovascular events (MACEs), Kaplan‒Meier curves were plotted. Serum SFRP5 levels were measured utilizing an enzyme-linked immunosorbent assay (ELISA) kit. The serum SFRP5 levels significantly decreased with the increasing severity and complexity of CAD, while the TyG index significantly increased (P < 0.001). Moreover, a significant negative correlation was observed between the serum SFRP5 levels and the TyG index (r = -0.312, P < 0.001). SFRP5 exerts a protective role in different groups of patients. The area under the receiver operating characteristic (ROC) curve indicated that an SFRP5 concentration > 115.58 pg/mL was the best predictive value for CAD (OR:0.87, P < 0.001). MACEs were significantly associated with serum SFRP5 levels and the TyG index, as indicated by both univariate and multivariate Cox regression analyses (P < 0.001). Furthermore, Kaplan‒Meier analysis indicated that as the TyG index decreased and SFRP5 levels increased, the occurrence of MACEs decreased (P < 0.001). Patients with a concentration of SFRP5 > 115.58 pg/mL and a TyG index < 8.49 exhibited a better prognosis for avoiding MACEs (P < 0.001). These results suggest that the collaboration between serum SFRP5 levels and the TyG index holds promise in predicting CAD and its prognosis.

The impact of serum and follicular fluid secreted frizzled-related protein-5 on ICSI outcome in Iraqi infertile women with different body mass index

Introduction and Aim: Adipose tissue adipokines and cytokines impede oocyte maturation and endometrial epithelial receptivity. Secreted frizzled-related protein 5 (Sfrp5), a novel antagonist adipokine secreted by adipocytes, may have anti-inflammatory and insulin-sensitizing actions, but data is conflicting. This study examined serum and follicular fluid Sfrp5 levels in Iraqi infertile women with varying BMIs undergoing IVF/ICSI, as well as ICSI outcomes. Materials and Methods: This prospective cross-sectional study comprised 90 infertile females aged 18–45 who underwent IVF/ICSI at the High Institute of Infertility Diagnosis and Assisted Reproductive Technologies Centre in Baghdad, Iraq. Participants received antagonist ovarian hyperstimulation. All individuals' blood fasting sugar, serum fasting insulin, serum, and follicular fluid SFRP5 were tested on oocyte retrieval day. HOMA-IR was computed. Oocyte maturity and embryo morphology were categorized. Serum B-hCG was measured 14 days after embryo transfer. Results: A notable disparity was observed in the levels of serum and follicular Sfrp5, total oocyte count, mean metaphase II (MII), grade I, and pregnancy rate (p&lt;0.05) among the participants categorized as normal weight, overweight, and obese. A notable disparity was observed in the average germinal vesicles (GV), grade III (GIII) embryos, and HOMA-IR (p &lt; 0.05) among patients with varying body mass index (BMI) values. The study found a positive correlation between the levels of Sfrp5 in both serum and follicular fluid and the total count of oocytes, MII oocytes, grade I embryos, and pregnancy rate. However, there was a negative correlation between Sfrp5 levels and HOMA-IR, with statistical significance at p&lt;0.05. Conclusion: Increased BMI is associated with lower serum and follicular fluid Sfrp5, reduced total oocyte count, reduced metaphase II oocyte count, more germinal vesicle oocytes, reduced embryo quality and lower pregnancy rate. Serum and follicular fluid Sfrp5 levels are negatively correlated with HOMA-IR but positively associated with ICSI outcome.

Association of Circulating Plasma Secreted Frizzled-Related Protein 5 (Sfrp5) Levels with Cardiac Function.

Secreted frizzled-related protein 5 (SFRP5) is a novel anti-inflammatory adipokine that may play a role in cardiovascular development and disease. However, there is yet to be a comprehensive investigation into whether circulating SFRP5 can be a biomarker for cardiac function. Plasma SFRP5 levels were measured via ELISA in 262 patients admitted to a cardiology unit. Plasma SFRP5 levels were significantly lower in patients with a history of heart failure (HF), coronary artery disease (CAD), and atrial fibrillation (AF; p = 0.001). In univariate analyses, SFRP5 levels were also significantly positively correlated with left ventricular ejection fraction (LVEF) (r = 0.52, p < 0.001) and negatively correlated with E/E' (r = -0.30, p < 0.001). Patients with HF, CAD, low LVEF, low triglycerides, high CRP, and high eGFR were associated with lower SFRP5 levels independent of age, BMI, or diabetes after multivariate analysis (overall model r = 0.729, SE = 0.638). Our results show that low plasma SFRP5 levels are independently associated with the presence of HF, CAD, and, importantly, impaired LV function. These results suggest a potential role of SFRP5 as a biomarker, as well as a mediator of cardiac dysfunction independent of obesity and metabolic regulation.

Human epicardial adipose tissue inflammation correlates with coronary artery disease.

This study investigates the expression of novel adipocytokines and inflammatory cells infiltration in epicardial adipose tissue (EAT) and subcutaneous adipose tissue (SAT) between 27 coronary artery disease (CAD) and 21 non-CAD (NCAD) patients enrolled from September 2020 to September 2021. Serum, gene, and protein expression levels of the novel adipocytokines were determined using ELISA, RT-qPCR, and western blot analyses. The number of blood vessels and adipocytes morphology were measured via hematoxylin-eosin staining, and inflammatory cells infiltration was examined via immunohistochemistry. Serum ANGPTL8, CTRP5, and Wnt5a levels were higher in the CAD than in the NCAD group, while serum CTRP3, Sfrp5, and ZAG levels were lower in the CAD than in the NCAD group. Compared to the EAT of NCAD and SAT of CAD patients, the EAT of CAD patients had higher mRNA levels of ANGPTL8, CTRP5, and Wnt5a while lower levels of CTRP3, Sfrp5, and ZAG; higher protein expression levels of ANGPTL8 and CTRP5 but lower levels of CTRP3; more blood vessels; and higher infiltration rates of macrophages (CD68+), pro-inflammatory M1 macrophages (CD11c+), mast cells (Tryptase+), T lymphocytes (CD3+), and B lymphocytes (CD20+) but lower infiltration rates of anti-inflammatory M2 macrophages (CD206+). Novel adipocytokines and inflammatory cells infiltration are dysregulated in human EAT, and could be important pathophysiological mechanisms and novelly promising medicating targets of CAD.

The effects of exercise training induced calories expenditure on type 2 diabetes related cardio metabolic physiological parameters and adipocytokines

BackgroundRecently, many studies have examined the effects of various training on pro-inflammatory and anti-inflammatory adipocytes. The results of these studies are contradictory. Some have reported positive effects and others have reported negative effects. However, there is no research to study the effect of exercise on similar energy expenditures on adipocytes. Hence the purpose of this study was the effects exercise training induced calories expenditure on type 2 diabetes related cardio metabolic physiological parameters and adipocytokines.MethodsSixty-eight men patients with type 2 diabetes [12 weeks] were randomized to 4 groups according to training regimens. the groups are [1] HIIT [n = 17], [2] RT[n = 17], [3] AT[n = 18], and [4] AT + RT n = 16]. For 12 weeks [4 days/week, 20–30 min/season], participants performed training sessions with 300 kcal energy expenditure. Before and after 12 weeks interventions, Anthropometric and physiological variables and Glucose, insulin, FFA, LDL, HDL, TG, TC collected and analyses. Leptin, SFRP5, LGR4 and Irisin levels in Serum were assessment by ELISA.ResultsSerum irisin concentrations were significantly higher in AT [%20.4] compared to other groups. Leptin, SFRP5 and LGR4 were significantly higher in HIIT [%-21.7, %48.1 and %30.9 respectively] compared to other groups. Serum SFRP5 concentrations were significantly increased in 4 groups[P > 0.05]. However, leptin and LGR4 were significantly decreased and increased in 3 groups expect in RT group[P > 0.05]. And irisin concentrations were significantly increased in AT group only[P > 0.05]. And many variables indicated positive and negative relationship between together [P > 0.05].ConclusionsThe findings of the present study showed that if exercised with energy expenditure equal to HIIT training, it has the greatest effect on improving inflammatory and anti-inflammatory indicators in type 2 diabetic patients, as well as glycemic and lipid-chemical variables.

Dipeptidylpeptidase (DPP)-4 inhibitor therapy increases circulating levels of anti-inflammatory soluble frizzle receptor protein (sFRP)-5 which is decreased in severe COVID-19 disease

Obesity and type 2 diabetes (T2D) show an increased risk for a severe COVID-19 disease. Treatment with DPP4 inhibitor (DPP4i) results in reduced mortality and better clinical outcome. Here, we aimed to identify potential mechanisms for the observed DPP4i effect in COVID-19. Comparing T2D subjects with and without DPP4i treatment, we identified a significant increase of the anti-inflammatory adipokine sFRP5 in relation to DPP4 inhibition. sFRP5 is a specific antagonist to Wnt5a, a glycopeptide secreted by adipose tissue macrophages acting pro-inflammatory in various diseases. We therefore examined sFRP5 levels in patients hospitalised for severe COVID-19 and found significant lower levels compared to healthy controls. Since sFRP5 might consequently be a molecular link for the beneficial effects of DPP4i in COVID-19, we further aimed to identify the exact source of sFRP5 in adipose tissue on cellular level. We therefore isolated pre-adipocytes, mature adipocytes and macrophages from adipose tissue biopsies and performed western-blotting. Results showed a sFRP5 expression specifically in mature adipocytes of subcutaneous and omental adipose tissue. In summary, our data suggest that DPP4i increase serum levels of anti-inflammatory sFRP5 which might be beneficial in COVID-19, reflecting a state of sFRP5 deficiency.

Circulating level of serum secreted frizzled-related protein 5 decreases in polycystic ovary syndrome

Objectives To analyse the SFRP-5 serum levels in PCOS and to investigate the relationship between SFRP-5 and other metabolic parameters in PCOS. Material and methods This is a prospective case–control study carried out in a research hospital. A total of 88 subjects including 43 patients diagnosed PCOS according to Rotterdam criteria and age –BMI matched 45 healthy controls were evaluated. Serum SFRP5, fasting blood glucose, insulin levels and HOMA-IR scores of the groups were determined and compared. The cut-off of SFRP-5 for detecting PCOS was calculated. Results Serum SFRP-5 levels were lower in PCOS group compared to the controls (290.13 ± 187.66 ng/mL vs 533.03 ± 208.55 ng/mL, p < 0.001). There was no correlation in the PCOS group regarding SFRP-5 and other parameters. The role of SFRP-5 to predict the PCOS risk was assessed with receiver operating curve (ROC). The sensitivity of SFRP-5 was 74.4% and the specificity was 75.6% at a threshold ≤388.38 ng/ml in PCOS. Conclusion SFRP-5 could be a beneficial marker for PCOS diagnosis, follow-up and treatment.

Decreased SFRP5 correlated with excessive metabolic inflammation in polycystic ovary syndrome could be reversed by metformin: implication of its role in dysregulated metabolism

BackgroundPolycystic Ovary Syndrome (PCOS) is a complex endocrine disorder of heterogeneous nature. Secreted frizzled-related protein (SFRP) 5 is an anti-inflammatory adipokine implicated in metabolic homeostasis. We aimed to confirm the correlation between SFRP5, metabolic inflammation and PCOS, investigate the predictive value of SFRP5 for PCOS and the involvement of SFRP5 in metformin treated PCOS.MethodsThis retrospective case–control study included 140 PCOS and 33 control women. Sixty seven PCOS women were included for detecting serum SFRP5 level and its correlation with metabolic inflammation. Predictive value of SFRP5 for PCOS was evaluated by logistic regression and receiver operating characteristic (ROC) analyses. Seventy three PCOS women complicated with impaired glucose tolerance (IGT)/insulin resistance (IR) were included for investigating the effects of metformin (37 with metformin vs. 36 without metformin) on SFRP5, pro-inflammatory cytokines, ovulation and pregnancy rate.ResultsPlasma SFRP5 levels were decreased in PCOS (odds ratio: 0.78, 95% confidence interval (CI):0.703–0.866, P < 0.001) independent of obesity. SFRP5 was negatively associated with IL-6, TNFα, FAI and HOMA-IR. The cut-off point of SFRP5 < 46.13 ng/ml was optimal to identify PCOS with a higher specificity of 96.87% and a relatively lower sensitivity compared to AMH. SFRP5 increased specificity of AMH for predicting PCOS, especially which with relatively decreased AMH (< 4.7 ng/ml). Metformin promoted SFRP5 and decreased leptin, IL-6 and TNFα secretion in PCOS women with metabolic abnormality in a time dependent manner and with improved ovulation rate and pregnancy rate.ConclusionDecreased SFRP5 was associated with metabolic inflammation in PCOS and has a potential role for the supplement of AMH in predicting PCOS. The reverse of serum SFRP5 by metformin indicated that SFRP5 participated in the improvment of follicular development by metformin. Further prospective investigations are needed to confirm these preliminary data.

Serum secreted frizzled-related protein 5 in relation to insulin sensitivity and its regulation by insulin and free fatty acids

PurposeSecreted frizzled-related protein 5 (SFRP5) is an adipokine, which acts as an inhibitor of noncanonical WNT signaling pathway. It has been suggested to exert anti-inflammatory and insulin-sensitizing effects, however, contradictory data has also been reported. The aim of this study was to assess serum SFRP5 concentration in a young healthy population in relation to insulin sensitivity and its regulation by hyperinsulinemia and/or serum free fatty acids (FFA) elevation.MethodsWe examined 150 healthy subjects (83 normal-weight and 67 overweight/obese). Insulin sensitivity (M) was measured with hyperinsulinemic-euglycemic clamp. In 20 male subjects, clamp was prolonged to 6 h and after 1 week another clamp with the concurrent Intralipid/heparin infusion was performed. Independent group of 10 male subjects received infusions of Intralipid/heparin or saline in 1-week interval.ResultsBaseline SFRP5 was lower in the overweight/obese group (p = 0.01) and was positively associated with M (r = 0.23, p = 0.006) and serum adiponectin (r = 0.55, p < 0.001) and negatively with BMI (r = −0.18, p = 0.03). In multiple regression analysis, adiponectin was independently associated with SFRP5. Insulin infusion resulted in a decrease in serum SFRP5, both at 120′ (p = 0.02) and 360′ (p = 0.031). This effect was not observed during the clamp with Intralipid/heparin as well as during Intralipid/heparin alone or saline infusions.ConclusionsThe relation between SFRP5 and insulin sensitivity is mainly dependent on adiponectin. FFA abolish a decrease in circulating SFRP5 caused by insulin, but Intralipid/heparin infusion alone does not regulate SFRP5 concentration. Insulin seems to be more important factor in the regulation of circulating SFRP5 levels than FFA.

Sfrp5/Wnt5a and leptin/adiponectin levels in the serum and the periarterial adipose tissue of patients with peripheral arterial occlusive disease

BackgroundLeptin, adiponectin, secreted frizzled-related protein 5 (Sfrp5) and wingless-type family member 5a (Wnt5a) are novel adipokines that are involved in insulin sensitivity and atherosclerosis. The aim of the present study was to investigate the serum and periarterial adipose tissue leptin/adiponectin and Sfrp5/Wnt5a levels in patients with peripheral arterial occlusive disease (PAOD). MethodsA total of 75 patients with PAOD and 39 control subjects were recruited. The serum concentrations of leptin, adiponectin, Sfrp5 and Wnt5a were measured by ELISAs, and the leptin, adiponectin, Sfrp5 and Wnt5a levels in the periarterial adipose tissue were observed by western blotting. ResultsThe serum Sfrp5 levels were significantly lower in the patients with PAOD than in the control subjects (p < 0.001) and Wnt5a levels were higher in the patients with PAOD (p < 0.001). The serum leptin levels were significantly higher in the patients with PAOD than in the control subjects (p < 0.001), and adiponectin levels were significantly lower in the patients with PAOD (p < 0.001). The serum Sfrp5 levels were associated with ABI (rs = 0.274; p = 0.018), Wnt5a (rs = −0.409; p < 0.001), adiponectin (rs = 0.244; p = 0.035) and Leptin/Adiponetin ratio (rs = −0.244; p = 0.037). The adiponectin and Sfrp5 protein levels were decreased in the periarterial adipose tissue of patients with PAOD compared with control subjects. The leptin and Wnt5a protein levels were increased in the periarterial adipose tissue of patients with PAOD compared with control subjects. ConclusionWe demonstrated that the adiponectin and Sfrp5 levels in the serum and periarterial adipose tissue were significantly lower in the patients with PAOD than in the control subjects. The leptin and Wnt5a levels in the serum and periarterial adipose tissue were significantly higher in the patients with PAOD than in the control subjects.

Reduction of Secreted Frizzled-Related Protein 5 Drives Vascular Calcification through Wnt3a-Mediated Rho/ROCK/JNK Signaling in Chronic Kidney Disease.

Vascular calcification (VC) is commonly associated with bone loss in patients with chronic kidney disease (CKD). The Wingless-related integration site (Wnt) regulates osteoblast activation through canonical signaling pathways, but the common pathophysiology of these pathways during VC and bone loss has not been identified. A rat model of adenine-induced CKD with VC was used in this study. The rats were fed 0.75% adenine (2.5% protein, 0.92% phosphate) with or without intraperitoneal injection of calcitriol (0.08 µg/kg/day) for 4 weeks. Angiotensin II (3 µM)-induced VC was achieved in high phosphate medium (3 mM) through its effect on vascular smooth muscle cells (VSMCs). In an mRNA profiler polymerase chain reaction assay of the Wnt signaling pathway, secreted frizzled-related protein 5 (sFRP5) levels were significantly decreased in the CKD rat model compared with the control group. The repression of sFRP5 on VSMC trans-differentiation was mediated through Rho/Rho-associated coiled coil containing protein kinase (ROCK) and c-Jun N-terminal kinase (JNK) pathways activated by Wnt3a. In a proof of concept study conducted with patients with CKD, serum sFRP5 concentrations were significantly lower in subjects with VC than in those without VC. Our findings suggest that repression of sFRP5 is associated with VC in the CKD environment via activation of the noncanonical Wnt pathway, and thus that sFRP5 might be a novel therapeutic target for VC in CKD.

Association of Adipocytokines With Carotid Intima Media Thickness and Arterial Stiffness in Obstructive Sleep Apnea Patients.

Objective: Obstructive sleep apnea (OSA) results in increased carotid intima-media thickness (IMT) and arterial stiffness; however, the association between adipocytokines and IMT/arterial stiffness in OSA patients is unclear.Methods: We enrolled 95 normal weight and overweight, not obese, participants from May 2018 to December 2018 in this study. All subjects underwent a carotid artery ultrasound examination and polysomnography. Blood samples were used to determine serum chemerin, adiponectin, SFRP5, and apelin levels. Correlations between two quantitative variables were assessed using the Pearson or Spearman coefficient. Stepwise models of multiple linear regression analysis were performed to assess the independent relationships.Result: IMT in OSA patients was significantly higher than in the non-snorers. There were significant differences in the arterial stiffness parameters such as distensibility coefficient (DC), compliance coefficient (CC), and pulse wave velocity (PWV). SFRP5 level was lower in OSA patients than in non-snorers. Adiponectin correlated with CC, DC, and PWV among OSA patients; however, the relationship disappeared after a multivariable adjustment. Age was independently associated with all quantitative IMT and stiffness indices. AHI and minimum oxygen saturation (Mini SaO2) were independently related to arterial stiffness.Conclusion: The quantitative IMT and carotid arterial elasticity were significantly worse among OSA patients. Age was the main independent factor correlated with quantitative IMT and arterial stiffness, and AHI and mini SaO2 were associated factors. There were no relationships between aforementioned adipocytokines and quantitative IMT/carotid arterial stiffness.

Expression of Sfrp5/Wnt5a in human epicardial adipose tissue and their relationship with coronary artery disease

Secreted frizzled-related protein 5 (Sfrp5) primarily acts in combination with wingless-type family member 5a (Wnt5a), to inhibits chronic inflammation and repress atherosclerosis and other metabolic disorders. Epicardial adipose tissue (EAT), surrounding the heart and coronary arteries, has been found to be highly related to the progression of coronary artery disease through adipokines production. However, little is known about EAT-derived Sfrp5 and Wnt5a in humans. We aimed to investigate whether the EAT-derived Sfrp5/Wnt5a levels are altered in patients with CAD. Fifty-eight patients with CAD and 29 patients without CAD who underwent cardiac surgery were enrolled. Serum samples and paired adipose biopsies from EAT and subcutaneous adipose tissue (SAT) were collected, and Sfrp5 and Wnt5a levels were detected. Correlation and multivariate regression analyses were performed to determine the relationship between Sfrp5/Wnt5a expression and CAD and other clinical risk factors.According to the results, the CAD group had lower Sfrp5 and higher Wnt5a levels in EAT and serum (all p < 0.05). Serum Sfrp5 levels were significantly lower in CAD patients with impaired myocardial function. EAT Sfrp5 mRNA levels and serum Sfrp5 levels were both negatively associated with the presence of CAD, after adjustment for known biomarkers, EAT mRNA and serum Wnt5a levels correlated positively with the presence of CAD.Thus, we concluded that low Sfrp5 and high Wnt5a levels are associated with the presence of CAD, independent of other conventional risk factors.

High Serum Secreted Frizzled-Related Protein 5 Levels Associates with Early Improvement of Cardiac Function Following ST-Segment Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention.

Aim: Several members of secreted frizzled-related protein (SFRP) are involved in the process of myocardial ischemia-reperfusion injury. However, little is known about the role of SFRP5 in patients with acute ST-segment elevation myocardial infarction (STEMI).Methods: In this cross-sectional study, 85 patients with first-time anterior STEMI who underwent timely primary percutaneous coronary intervention (PCI) and 35 patients without coronary artery disease (CAD) were enrolled. Serum SFRP5 levels were measured using an enzyme-linked immunosorbent assay kit. Patients with STEMI were divided into low-SFRP5 and high-SFRP5 groups according to their median baseline serum SFRP5 levels. To evaluate cardiac function and structure after infarction, the left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume (LVEDV) were measured using echocardiography. The associations between changes in LVEF and reduced LVEF (≤ 50%) and clinical variables were determined by univariate and multivariate analyses.Results: Baseline serum SFRP5 levels were significantly higher in patients with STEMI than in those without CAD (23.3 ng/mL vs 19.8 ng/mL, P = 0.008), although they decreased over time. Also, baseline serum SFRP5 levels were inversely correlated with peak hypersensitive cardiac troponin I (hs-cTnI) levels (r = −0.234, P = 0.025) and peak hypersensitive C-reactive protein (hs-CRP) levels (r = −0.262, P = 0.015). A multivariate linear regression model showed that changes in LVEF were positively correlated with serum SFRP5 levels at baseline (β = 0.249, 95% confidence interval (CI) 0.018–0.245, P = 0.024) and 24 h after admission (β = 0.220, 95% CI 0.003–0.264, P = 0.045). At 3 months, LVEF in patients with high SFRP5 levels was significantly improved over baseline [(60.8 ± 7.1) % vs (56.1 ± 7.5) %, P = 0.001]. LVEF was also significantly higher in patients with high SFRP5 levels than in those with low at the 3-month follow-up [(60.8 ± 7.1) % vs (56.8 ± 8.9) %, P = 0.028]. Consequently, high serum SFRP5 levels at baseline were associated with a decreased risk of reduced LVEF at 3 months, independent of peak hs-cTnI and baseline cardiac function (hazard ratio 0.190, 95% CI 0.036–0.996; P = 0.049).Conclusions: High serum SFRP5 levels measured during the acute phase of STEMI were significantly associated with promoting myocardial recovery at an early phase following primary PCI, suggesting that SFRP5 is a potential therapeutic target in acute STEMI.

Correlations between the levels of serum Wnt5a, Sfrp5, and glycemic control in elderly male patients with type 2 diabetes mellitus

Objective To investigate the levels of serum Wnt5a and Sfrp5 in elderly male patients with type 2 diabetes mellitus (T2DM), and identify associations between their levels and glycemic control. Methods A total of 67 elderly male T2DM patients and 65 nondiabetic subjects were studied. Participants were divided into four groups: normal control (NC group), T2DM patients were categorized by HbA1C quartile(Group Ⅰ: HbA1C<7%, Group Ⅱ: 7%≤HbA1C<9%, Group Ⅲ: HbA1C≥9%). The serum Wnt5a and Sfrp5 concentrations were measured through ELISA. Influencing factors for Wnt5a and Sfrp5 were analyzed. Results Compared with the NC group, Wnt5a levels of elderly T2DM were decreased in groups Ⅱ and Ⅲ, in contrast, Sfrp5 levels were elevated in groups Ⅱ and Ⅲ than NC group(all P<0.05). Spearman correlation analysis suggested that Wnt5a levels were negatively correlated with HbA1C, GA, FPG, and 2hPG(r were -0.277, -0.298, -0.185, and -0.254 respectively, all P<0.05); Sfrp5 levels were positively correlated with HbA1C, GA, and FPG(r were 0.311, 0.247, and 0.200 respectively, all P<0.05) while negatively correlated with BMI and LDL-C(r were -0.193 and -0.190, both P<0.05). Multivariate linear regression analysis showed that HbA1C was an independent association factor for Wnt5a, and FPG was an independent association factor for Sfrp5. Conclusions In the elderly male T2DM with worse glycemic control, Wnt5a levels were more decreased, and in contrast, Sfrp5 levels were elevated. This result indicated that Wnt5a and Sfrp5 may be associated with the level of glycemic control in elderly male T2DM patients. (Chin J Endocrinol Metab, 2018, 34: 904-908) Key words: Diabetes mellitus, type 2; Wingless-type MMTV integration site family, member 5A; Secreted frizzled-related protein 5; Glycemic control

Type 2 diabetes with hypertensive patients results in changes to features of adipocytokines: Leptin, Irisin, LGR4, and Sfrp5

ABSTRACTThe incidence of hypertension and diabetes is increasing, it is reported that adipocytokines might be involved in the pathogenesis of diabetes and hypertension. We aimed to investigate the features of adipocytokines, included of Leptin, Irisin, LGR4, and Sfrp5 in type 2 diabetes mellitus (T2DM) patients with hypertension, simultaneously analyzed the connection of the alteration of adipocytokines with blood pressure and glucose. 424 patients with T2DM and 90 healthy subjects were included in the study. The patients with T2DM were divided into 4 groups based on the blood pressure. The levels of adipocytokines (Leptin, Irisin, LGR4, and Sfrp5) were determined by enzyme-linked immunosorbent assay (ELISA). Significantly higher levels of Leptin and lower levels of Irisin, LGR4 and Sfrp5 were seen in patients with diabetes compared with non-diabetes (P < 0.05), the mean values of Leptin level was ascending and Irisin, LGR4, and Sfrp5 levels were declining with promoting of blood pressure in hypertension as compared to the non-hypertension with diabetic patients. Multiple stepwise linear regression analysis showed that the concentrations of Leptin, Irisin, Sfrp5, and LGR4 were found to be closely associated with the control of blood pressure and glucose. Conclusion: Four adipocytokines might play different roles and closely relate to the occurrence and development of diabetes and hypertension.

The effect of serum and follicular fluid secreted frizzle-related protein-5 on in vitro fertilization outcomes in patients with polycystic ovary syndrome.

In this study, we aimed to investigate serum and follicular fluid (FF) secreted frizzle-related protein-5 (Sfrp-5) levels in nonobese, nonhyperandrogenic patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF), in addition to IVF outcomes. In total, 160 patients undergoing IVF treatment were included in the study: 80 patients diagnosed with PCOS according to the Rotterdam criteria (group I, study) and 80 patients with the etiology of male factor infertility (group II, control). There were statistically significant between-group differences in serum estradiol (E2) levels on the day of hCG administration (2377.00 ± 733.23 vs. 1931.3 ± 1,010.69), the total gonadotropin dose required (2000.63 ± 1,051.87 vs. 1.134.69 ± 286.45), and the total number of retrieved oocytes (8.60 ± 2.06 vs. 11.05 ± 4.39) (p < 0.05). There was also a statistically significant between-group difference in serum and FF Sfrp-5 levels on the day of oocyte retrieval (11.40 ± 2.88 vs. 8.87 ± 1.85, p < 0.001; 11.06 ± 2.30 vs. 9.71 ± 2.15, p = 0.008; respectively). However, there were no between-group differences in fertilization rates, clinical pregnancy rates, and live birth rates (p > 0.05). A correlation analysis showed that serum and FF Sfrp-5 levels were associated with insulin and inflammatory markers (p < 0.05). In a selected population of nonobese, nonhyperandrogenic PCOS patients, there was a significant difference in Sfrp-5 levels of the PCOS group versus those of the control group. Further studies are needed to determine the effects of Sfrp-5 in women with PCOS.

Circulating secreted frizzled-related protein 5 and chronic kidney disease in patients with acute ST-segment elevation myocardial infarction

Secreted frizzled-related protein-5 (Sfrp5) known as secreted antagonist binds to Wnt protein. It has been shown to be downregulated by histone acetylation and promoter methylation, and to function as a tumor suppressor gene by inducing apoptosis in renal cell cancer cells. However, its relationship with chronic kidney disease (CKD) has not been well studied. Our objective was to investigate the effect of plasma Sfrp5 levels in subjects with and without CKD. Plasma Sfrp5 levels were determined by enzyme-linked immunosorbent assays in 196 consecutive patients with acute ST-segment elevation myocardial infarction (STEMI). CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2. For the purpose of this study, stage 1 or 2 CKD patients (eGFR ≥ 60 ml/min per 1.73 m2) were classified as not having CKD. With increasing Sfrp5 tertiles, the patients had higher frequencies of hypertension, stage 4 or 5 CKD, and waist-to-hip ratio, incrementally lower eGFRs and serum hemoglobin levels, and higher levels of blood urine nitrogen (BUN), creatinine, and adiponectin. Multivariate logistic regression analysis showed that an increased plasma Sfrp5 level was independently associated with CKD for all subjects (adjusted odds ratio (OR), 1.08; 95% confidence interval (CI), 1.02–1.14; p = 0.011). Sfrp5 was also significantly positively related to BUN, creatinine, and adiponectin, and significantly negatively related to eGFR and hemoglobin. When the patients were stratified by age, plasma Sfrp5 level was independently related to CKD for patients >65 years old (adjusted OR, 1.10; 95% CI, 1.00–1.20; p = 0.045), however, the association was not significant for those <65 years old. In addition, Sfrp5 was significantly positively related to BUN, creatinine, and adiponectin, and significantly negatively related to eGFR and hemoglobin in patients >65 years old. Our results suggest that Sfrp5 may play a role in the pathogenesis of CKD in acute STEMI patients who are older than 65 years.