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Background The relationship between plasma lipoprotein lipase (LPL), hepatic triglyceride lipase (HTGL), glycosylphosphatidylinositol anchored HDL binding protein1 (GPIHBP1) concentration and the metabolism of remnant lipoproteins (RLP) and small dense LDL (sdLDL) in patients with coronary artery disease (CAD) is not fully elucidated. Methods One hundred patients who underwent coronary angiography were enrolled. The plasma LPL, HTGL and GPIHBP1 concentrations were determined by ELISA. The time dependent changes in those lipases, lipids and lipoproteins were studied at a time-point just before, and 15 min, 4 h and 24 h after heparin administration. Results The LPL concentration exhibited a significant positive correlation with HDL-C, and inversely correlated with TG and RLP-C. The HTGL concentration was positively correlated with RLP-C and sdLDL-C. The HTGL ratio of the pre-heparin/post-heparin plasma concentration and sdLDL-C/LDL-C ratio were significantly greater in CAD patients than in non-CAD patients. GPIHBP1 was positively correlated with LPL and inversely correlated with RLP-C and sdLDL-C. Conclusion The HTGL concentration was positively correlated with RLP-C and sdLDL-C, while LPL and GPIHBP1 were inversely correlated with RLP-C and sdLDL-C. These results suggest that elevated HTGL is associated with increased CAD risk, while elevated LPL is associated with a reduction of CAD risk. [ABSTRACT FROM AUTHOR]

Background Solute carrier family 5 member A8 ( SLC5A8 ) is a sodium-coupled transporter for several chemicals. The SLC5A8 gene has been reported to function as a tumor suppressor gene that contributes to carcinogenesis and tumor progression. The expression of SLC5A8 is silenced in colon neoplasia by hypermethylation of CpG-rich islands located in exon 1. In this study, we assessed the significance of aberrant methylation of the SLC5A8 gene as a prognostic factor for lung adenocarcinoma (AD). Methods We analyzed the methylation levels of a consecutive series of 143 node-negative stage I and II lung AD samples using pyrosequencing. Results The methylation level of exon 1 in the SLC5A8 gene was significantly associated with poor prognosis in cases of node-negative stage I and II lung AD. Conclusions Gene silencing of SLC5A8 by hypermethylation was associated with poor prognosis in cases of node-negative stage I and II lung AD. [ABSTRACT FROM AUTHOR]

To investigate the mechanisms of the hypolipidemic effect ofmonatepil, a new class of calcium antagonists withα1-adrenergic blocking activity, we examined theeffects of the drug on low-density lipoprotein (LDL) receptor activity andthe level of LDL receptor mRNA present in cultured human skin fibroblasts.At concentrations of 2 × 10−5M, monatepilincreased the binding (248 ± 43% mean ± SD),internalization (374 ± 18%), and degradation (145 ±2%) of 125I-LDL in human skin fibroblasts (n =3, p<0.05). Treatment of human skin fibroblasts with 2 × 10−5 M of monatepil for 6 hours resulted in an increasein LDL receptor mRNA to 163% of the control level (n = 2), asshown by Northern blot analysis. Our results suggest that the hypolipidemicclinical effects of monatepil may be due to increased LDL receptoractivity. [ABSTRACT FROM AUTHOR]

Abstract Background Lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) play a central role in triglyceride-rich lipoprotein metabolism by catalyzing the hydrolysis of triglycerides. Quantification of LPL and HTGL activity is useful for diagnosing lipid disorders, but there has been no automated method for measuring these lipase activities. Methods The automated kinetic colorimetric method was used for assaying LPL and HTGL activity in the post-heparin plasma using the natural long-chain fatty acid 2-diglyceride as a substrate. LPL activity was determined with apoCII and HTGL activity was determined without apoCII with 2 channel of auto-analyzer. Results The calibration curve for dilution tests of the LPL and HTGL activity assay ranged from 0.0 to 500 U/L. Within-run CV was obtained within a range of 5%. No interference was observed in the testing of specimens containing potentially interfering substances. The measurement range of LPL activity in the post-heparin plasma was 30–153 U/L, while HTGL activity was 135–431 U/L in normal controls. Conclusions The L PL and HTGL activity assays are applicable to quantitating the LPL and HTGL activity in the post-heparin plasma. This assay is more convenient and faster than radiochemical assay and highly suitable for the detection of lipid disorders. Highlights • Automated and simultaneous LPL and HTGL activity assay in plasma was developed. • The L PL and HTGL activity is suitable to detect in 15 min in post-heparin plasma. • Both activities decreased to basal levels in 90 min after heparin administration. • Both activities were detectable in patient plasma under cardiac catheter test. [ABSTRACT FROM AUTHOR]

There is no established method for measuring human hepatic triglyceride (TG) lipase (HTGL) concentration in serum. In this study, we developed new monoclonal Abs (MoAbs) (9A1 mouse MoAb and 141A1 rat MoAb) that react with HTGL both in serum and in postheparin plasma (PHP) and established a novel ELISA system for measuring serum HTGL and PHP-HTGL concentrations. To confirm the specificity of MoAbs, we performed immunoprecipitation-immunoblotting analysis. Both 9A1 mouse MoAb and 141A1 rat MoAb were able to immunoprecipitate not only recombinant HTGL and PHP-HTGL but also serum HTGL, demonstrating that HTGL exists in serum obtained without heparin injection. This method yielded intra- and interassay coefficients of variation of <6% and showed no cross-reactivity with LPL or endothelial lipase. In clinical analysis on 42 male subjects with coronary artery disease, there were strong positive correlations of serum HTGL concentration to PHP-HTGL concentration ( r = 0.727, P < 0.01). Serum HTGL concentrations showed positive correlations to serum TGs ( r = 0.314, P < 0.05) and alanine aminotransferase ( r = 0.406, P < 0.01), and tendencies toward positive correlations to LDL cholesterol, small dense LDL, and γGTP. These results suggest that this new ELISA method for measuring serum HTGL is applicable in daily clinical practice., (Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.)

A number of in vitro studies have suggested potential pathophysiological roles of human (h-) chymase. However, the lack of an appropriate animal model has left the in vivo roles of chymase unclear. To approach this problem, a transgenic mouse (TGM) model carrying the h-chymase gene was established. The h-chymase cDNA transgene was constructed with the chicken beta actin promoter and cytomegalovirus immediate early gene enhancer, and injected into mouse oocytes. Homozygous mice with a high copy number of the h-chymase gene suffered from intrauterine death. In three heterozygous TGM lines, h-chymase transgene expression was detected in entire organs, including the heart, vessels, skin, liver, lung, and brain. The h-chymase immunoreactivity was localized in the extracellular matrices of each organ, especially on the basement membranes of vessels. Aortic and hepatic chymase-dependent angiotensin II formations were significantly higher than those in the wild-type littermates. Three independent TGM lines showed the same phenotypic changes: elevation of blood pressure, left ventricular hypertrophy, emaciation with reduction in the lipid tissue, leukocytosis, and oligotrichia. The angiotensin II subtype 1 (AT1) receptor antagonist valsartan suppressed the elevated blood pressure completely and left ventricular hypertrophy incompletely, but did not affect the other phenotypes. These data suggested that in vivo expression of h-chymase caused mild hypertension (AT1 receptor-dependent) with left ventricular hypertrophy (partially AT1 receptor-dependent), and also chronic inflammatory changes (AT1 receptor-independent).