Background: The serum level of fatty-acid-binding protein 4 (FABP4) increases in patients with metabolic syndrome (MetS), so the relationship between FABP4 and MetS among patients with coronary artery disease (CAD) was investigated in the present study. Methods and Results: Fasting blood samples were obtained from 98 CAD patients. MetS and its components were defined using the diagnostic criteria of the International Diabetes Federation; 50 CAD patients (51.0%) had MetS. The fasting level of FABP4 positively correlated with MetS (P=0.037) and serum levels of FABP4 correlated with a number of MetS criteria (P=0.035). Univariate linear regression analysis showed that body fat mass (R=0.234; P=0.020) and the levels of triglycerides (R=0.348; P<0.001), and low-density lipoprotein-cholesterol (R=0.217; P=0.032) positively correlated with the serum level of FABP4, whereas the level of high-density lipoprotein-cholesterol (R=-0.243; P=0.016) negatively correlated with it. Multivariate forward stepwise linear regression analysis of the significant variables showed that the level of triglycerides (β=0.348, R2=0.121, P<0.001) was the independent predictor of fasting serum level of FABP4. Conclusions: Among CAD patients in the present study, the fasting level of FABP4 positively correlated with MetS and serum levels of FABP4 correlated with a number of MetS criteria. (Circ J 2010; 74: 327-331)

Vascular calcification (VC) is associated with increased cardiovascular risks in patients with chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibitors, such as empagliflozin, can improve cardiovascular and renal outcomes. We assessed the expression of Runt-related transcription factor 2 (Runx2), interleukin (IL)-1β, IL-6, AMP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor (Nrf2), and heme oxygenase 1 (HO-1) in inorganic phosphate-induced VC in mouse vascular smooth muscle cells (VSMCs) to investigate the mechanisms underlying empagliflozin’s therapeutic effects. We evaluated biochemical parameters, mean artery pressure (MAP), pulse wave velocity (PWV), transcutaneous glomerular filtration rate (GFR), and histology in an in vivo mouse model with VC induced by an oral high-phosphorus diet following a 5/6 nephrectomy in ApoE^−/− mice. Compared to the control group, empagliflozin-treated mice showed significant reductions in blood glucose, MAP, PWV, and calcification, as well as increased calcium and GFR levels. Empagliflozin inhibited osteogenic trans-differentiation by decreasing inflammatory cytokine expression and increasing AMPK, Nrf2, and HO-1 levels. Empagliflozin mitigates high phosphate-induced calcification in mouse VSMCs through the Nrf2/HO-1 anti-inflammatory pathway by activating AMPK. Animal experiments suggested that empagliflozin reduces VC in CKD ApoE^−/− mice on a high-phosphate diet.

Wnt/β-catenin signaling pathway is thought to be implicated in the development of arterial stiffness and vascular calcification. As a Wnt signaling pathway inhibitor, it is interesting to investigate whether sclerostin or dickkopf-1 (DKK1) level is correlated with arterial stiffness in renal transplant (RT) recipients. Fasting blood samples were obtained for biochemical data, sclerostin, DKK1, and osteoprotegerin (OPG) determinations. In this study, we applied automatic pulse wave analyzer (VaSera VS-1000) to measure brachial-ankle pulse wave velocity and either sides of brachial-ankle pulse wave velocity value, which greater than 14.0 m/s was determined as high arterial stiffness. Among 68 RT recipients, 30 patients (44.1%) were in the high arterial stiffness group. Compared with patients in the low arterial stiffness group, patients in the high arterial stiffness group had higher prevalence of hypertension (P = 0.002), diabetes (P < 0.001), metabolic syndrome (P = 0.025), longer posttransplant duration (P = 0.005), higher systolic blood pressure (P < 0.001) and diastolic blood pressure (P = 0.018), and higher fasting glucose (P = 0.004), total cholesterol (P = 0.042), blood urea nitrogen (P = 0.020), phosphorus (P = 0.042), and sclerostin levels (P = 0.001). According to our multivariable forward stepwise linear regression analysis, age (β = 0.272, P = 0.014), phosphorus (β = 0.308, P = 0.007), and logarithmically-transformed OPG (log-OPG; β = 0.222, P = 0.046) were positively associated with sclerostin levels, and multivariate logistic regression analysis, sclerostin (odds ratio 1.052, 95% confidence interval 1.007–1.099, P = 0.024), and posttransplant duration (odds ratio 1.024, 95% confidence interval 1.004–1.045, P = 0.019) were the independent predictors of peripheral arterial stiffness in RT recipients. In this study, serum sclerostin level, but not DKK1, was proved to be involved in the pathogenetic process of peripheral arterial stiffness in RT recipients.

Adiponectin has been implicated in metabolic syndrome (MetS) and arterial stiffness (AS). We aim to determine the relationship between serum adiponectin concentration as well as peripheral AS in hypertensive patients. Fasting blood samples were obtained from 101 hypertensive patients. Brachial-ankle pulse wave velocity (baPWV) was measured with an automatic pulse wave analyzer. Serum adiponectin concentrations were determined by using an enzyme immunoassay kit. A baPWV >14.0 m/s was defined as high AS. MetS and high AS were present in 62.4 and 71.3% of the study population. Adiponectin was inversely associated with MetS and high AS (both P < 0.001). Serum higher high-density lipoprotein cholesterol (HDL-C) (P = 0.012), triglycerides (P = 0.001), C-reactive protein (P < 0.001), insulin (P = 0.027), body weight (P = 0.002), waist circumference (WC, P < 0.001), body mass index (P = 0.001) bilateral-baPWV (P < 0.001), systolic blood pressure (SBP, P < 0.001), diastolic blood pressure (DBP, P = 0.012), pulse pressure (P = 0.019), homeostasis model assessment of insulin resistance (HOMA1-IR (P = 0.026) and HOMA2-IR (P = 0.020)) and lower glomerular filtration rate (GFR, P = 0.029) were significantly associated with high AS. Multivariate logistic regression analysis of the factors significantly associated with AS revealed that adiponectin [odds ratio: 0.932, 95% confidence interval (CI) 0.881–0.985, P = 0.012], and SBP (odds ratio: 1.059, 95% CI 1.008–1.113, P = 0.022) were the independent predictors of arterial stiffness in hypertensive patients. Subgroup analysis revealed that SBP (odds ratio: 1.126, 95% CI 1.024–1.237, P = 0.014) and GFR (odds ratio: 0.858, 95% CI 0.739–0.996, P = 0.043) were the independent predictors of arterial stiffness in hypertensive patients without MetS; adiponectin (odds ratio: 0.909, 95% CI 0.931–0.996, P = 0.040) was the independent predictor of arterial stiffness in hypertensive patients with MetS. Hypoadiponectinemia has positive association with MetS and peripheral AS in hypertensive patients.