In contrast with other antihypertensive drugs, olmesartan may uniquely increase urinary ACE2 level, which could potentially offer additional renoprotective effects.

ObjectiveFatty acid-binding proteins (FABPs) are a family of 14-15-kDa proteins, and some FABPs have been to be used as biomarkers of tissue injury by leak from cells. However, recent studies have shown that FABPs can be secreted from cells into circulation. Here we examined determinants and roles of circulating FABPs in a general population.MethodsFrom the database of the Tanno-Sobetsu Study, a study with a population-based cohort design, data in 2011 for 296 subjects on no medication were retrieved, and FABP1∼5 in their serum samples were assayed.ResultsLevel of FABP4, but not the other isoforms, showed a gender difference, being higher in females than in males. Levels of all FABPs were negatively correlated with estimated glomerular filtration rate (eGFR), but a distinct pattern of correlation with other clinical parameters was observed for each FABP isoform; significant correlates were alanine aminotransferase (ALT), blood pressure (BP), and brain natriuretic peptide (BNP) for FABP1, none besides eGFR for FABP2, age, BP, and BNP for FABP3, age, waist circumference (WC), BP, BNP, lipid variables, high-sensitivity C-reactive protein (hsCRP), and HOMA-R for FABP4, and age, WC, BP, ALT, BNP, and HOMA-R for FABP5. FABP4 is the most strongly related to metabolic markers among FABPs. In a multivariate regression analysis, FABP4 level was an independent predictor of HOMA-R after adjustment of age, gender, WC, BP, HDL cholesterol, and hsCRP.ConclusionsEach FABP isoform level showed a distinct pattern of correlation with clinical parameters, although levels of all FABPs were negatively determined by renal function. Circulating FABP4 appears to be a useful biomarker for detecting pre-clinical stage of metabolic syndrome, especially insulin resistance, in the general population.

Objective: Fatty acid-binding protein 4 (FABP4) is expressed in adipocytes, and elevated plasma FABP4 levels are associated with obesity-mediated metabolic phenotype. Postprandial regulation and secretory signaling of FABP4 have been investigated. Methods: Time courses of FABP4 levels were examined during an oral glucose tolerance test (OGTT; n 5 53) or a high-fat test meal (n 5 35). Effects of activators and inhibitors of adenyl cyclase (AC)-protein kinase A (PKA) signaling and guanylyl cyclase (GC)-protein kinase G (PKG) signaling on FABP4 secretion from mouse 3T3-L1 adipocytes were investigated. Results: FABP4 level significantly declined after the OGTT or a high-fat meal, while insulin level was increased. Treatment with low and high glucose concentration or palmitate for 2 h did not affect FABP4 secretion from 3T3-L1 adipocytes. FABP4 secretion was increased by stimulation of lipolysis using isoproterenol, a b 3 -adrenoceptor agonist (CL316243), forskolin, dibutyryl-cAMP, and atrial natriuretic peptide, and the induced FABP4 secretion was suppressed by insulin or an inhibitor of PKA (H-89), PKG (KT5823), or hormone sensitive lipase (CAY10499). Conclusions: FABP4 is secreted from adipocytes in association with lipolysis regulated by AC-PKA-and GC-PKG-mediated signal pathways. Plasma FABP4 level declines postprandially, and suppression of FABP4 secretion by insulin-induced anti-lipolytic signaling may be involved in this decline in FABP4 level.

Aims Previously, we determined the phenotyping of in vivo nicotine metabolism and the genotyping of the CYP2A6 gene ( CYP2A6 * 1 A , CYP2A6 * 1B , CYP2A6 * 2 , CYP2A6 * 3, CYP2A6 * 4 and CYP2A6 * 5 ) in 92 Japanese and 209 Koreans. In the study, we found one Korean and four Japanese subjects genotyped as CYP2A6 * 1B/CYP2A6 * 4 who revealed impaired nicotine metabolism, although other many heterozygotes of CYP2A6 * 4 demonstrated normal nicotine metabolism ( CYP2A6 * 4 is a whole deletion type). After our previous report, several CYP2A6 alleles, CYP2A6 * 6 (R128Q) , CYP2A6 * 7 (I471T) , and CYP2A6 * 8 (R485L), have been reported. The purpose of the present study was to clarify whether the impaired nicotine metabolism can be ascribed to these CYP2A6 alleles. Furthermore, we also determined whether the subjects possessing CYP2A6 * 1 ¥ 2 (duplication) reveal higher nicotine metabolism. Methods Genotyping of CYP2A6 alleles, CYP2A6 * 6, CYP2A6 * 7, CYP2A6 * 8 , and CYP2A6 * 1 ¥ 2 was determined by PCR. Results The five poor metabolizers were re-genotyped as CYP2A6 * 7/CYP2A6 * 4 , suggesting that a single nucleotide polymorphism (SNP) causing I471T decreases nicotine metabolism in vivo . Furthermore, we found that two subjects out of five with a lower potency of nicotine metabolism possessed SNPs of CYP2A6 * 7 and CYP2A6 * 8 simultaneously. The novel allele was termed CYP2A6 * 10 . In the 92 Japanese and 209 Koreans, the CYP2A6 * 6 allele was not found. The allele frequencies of CYP2A6 * 7 , CYP2A6 * 8, and CYP2A6 * 10 were 6.5%, 2.2%, and 1.1%, respectively, in Japanese, and 3.6%, 1.4%, and 0.5%, respectively, in Koreans. The CYP2A6 * 1 ¥ 2 allele was found in only one Korean subject (0.5%) whose nicotine metabolic potency was not very high. Conclusions It was clarified that the impaired in vivo nicotine metabolism was caused by CYP2A6 * 7 and CYP2A6 * 10 alleles.

FABP4 locally produced by epicardial/perivascular fat and macrophages in vascular plaques contributes to the development of coronary atherosclerosis.

Background: Fatty acid-binding protein 4 (FABP4) is expressed in both adipocytes and macrophages. Recent studies have shown secretion of FABP4 from adipocytes and association of elevated serum FABP4 level with obesity, insulin resistance, hypertension, and atherosclerosis. However, little is known about role of FABP4 in cardiac function. Methods: From the database of the Tanno-Sobetsu Study, data for 190 subjects (male/female: 82/108) who were not treated with any medication and underwent echocardiography in 2011 or 2012 were retrieved for analyses of relationships between serum FABP4 concentration, metabolic markers and parameters of echocardiography. Results: Serum FABP4 level was positively correlated with age, body mass index (BMI), blood pressure (BP), LDL cholesterol, HOMA-R and mean left ventricular (LV) wall thickness (LVWT, males: r = 0.315, females: r = 0.401, p < 0.01) and was negatively correlated with HDL cholesterol, estimated glomerular filtration rate (eGFR) and peak myocardial velocity during early diastole (e'; males: r = −0.434, females: r = −0.353, p < 0.01), an index of LV diastolic function. However, no significant correlation was found between FABP4 level and LV end-diastolic dimension, LV ejection fraction or LV mass index. There were significant correlations of e' with age, BMI, BP, eGFR, brain natriuretic peptide (BNP), FABP4, metabolic markers and LVWT. Multivariate regression analysis adjusted by HOMA-R, BMI, eGFR, BNP or LVWT in addition to age, gender and BP revealed that serum FABP4 concentration was independently correlated with e'. Conclusions: Elevation of circulating FABP4 may contribute to LV diastolic dysfunction in a general population.

BackgroundFatty acid‐binding protein 4 (FABP4) is expressed in adipocytes, macrophages, and endothelial cells of capillaries but not arteries. FABP4 is secreted from adipocytes in association with lipolysis, and an elevated circulating FABP4 level is associated with obesity, insulin resistance, and atherosclerosis. However, little is known about the link between FABP4 and endovascular injury. We investigated the involvement of ectopic FABP4 expression in endothelial cells in neointima hyperplasia after vascular injury.Methods and ResultsFemoral arteries of 8‐week‐old male mice were subjected to wire‐induced vascular injury. After 4 weeks, immunofluorescence staining showed that FABP4 was ectopically expressed in endothelial cells of the hyperplastic neointima. Neointima formation determined by intima area and intima to media ratio was significantly decreased in FABP4‐defficient mice compared with that in wild‐type mice. Adenovirus‐mediated overexpression of FABP4 in human coronary artery endothelial cells (HCAECs) in vitro increased inflammatory cytokines and decreased phosphorylation of nitric oxide synthase 3. Furthermore, FABP4 was secreted from HCAECs. Treatment of human coronary smooth muscle cells or HCAECs with the conditioned medium of Fabp4‐overexpressed HCAECs or recombinant FABP4 significantly increased gene expression of inflammatory cytokines and proliferation‐ and adhesion‐related molecules in cells, promoted cell proliferation and migration of human coronary smooth muscle cells, and decreased phosphorylation of nitric oxide synthase 3 in HCAECs, which were attenuated in the presence of an anti‐FABP4 antibody.ConclusionsEctopic expression and secretion of FABP4 in vascular endothelial cells contribute to neointima formation after vascular injury. Suppression of ectopic FABP4 in the vascular endothelium would be a novel strategy against post‐angioplasty vascular restenosis.

We report a novel human adenovirus D (HAdV-65) isolated from feces of 4 children in Bangladesh who had acute gastroenteritis. Corresponding genes of HAdV-65 were related to a hexon gene of HAdV-10, penton base genes of HAdV-37 and HAdV-58, and a fiber gene of HAdV-9. This novel virus may be a serious threat to public health.