Efecto de la inhibición de la proteína símil angiopoyetina tipo 3 (ANGPTL3): utilidad para el tratamiento de las dislipemias graves / Angiopoietin-like type 3 (angptl) inhibition: its role in the treatment of severe dyslipidemia

Las variantes de ANGPTL3 con pérdida de función están asociadas con efectos beneficiosos sobre el metabolismo lipídico y de carbohidratos y con riesgo reducido de enfermedad coronaria. Los cambios beneficiosos en los parámetros lipídicos que se obtienen con la inhibición de ANGPTL3 junto con la reducción en aterosclerosis que se observa en modelos animales y en estudios epidemiológicos de genética humana hacen de ANGPTL3 un nuevo objetivo terapéutico para prevenir las enfermedades cardiovasculares. Dos estrategias novedosas han surgido para inhibir esta proteína: un anticuerpo monoclonal y un oligonucleótido antisentido, con capacidad para reducir tanto el colesterol como los triglicéridos plasmáticos en forma notoria. Aunque el horizonte es promisorio, todavía no sabemos si los efectos de una variante presente desde el comienzo de la vida serán reproducidos por la inhibición de esta proteína que se realiza más tarde en la vida a través de una intervención farmacológica. (AU)

Loss-of-function ANGPTL3 variants are associated with beneficial effects on carbohydrate and lipid metabolism, and reduced risk of coronary heart disease. The beneficial changes in lipid parameters obtained by ANGPTL3 inhibition together with atheroprotection observed in animal models and in epi-demiological studies of human genetics make ANGPTL3 a new therapeutic target to prevent cardiovascular diseases. Two novel strategies have emerged to inhibit this protein: a monoclonal antibody and an antisense oligonucleotide, with the ability to significantly lower plasma cholesterol and triglycerides. Although the horizon is promising, we still do not know if the effects of a variant present from the beginning of life will be reproduced by the inhibition of this protein that takes place later in life through a pharmacological intervention. (AU)

Betatrophin Levels were Increased in Pregnant Women with or without Gestational Diabetes Mellitus and Associated with Beta Cell Function / Níveis de betatrofina aumentados em grávidas com ou sem diabetes mellitus gestacional e associados à função das células beta

Abstract Purpose betatrophin has been reported to boost β cell expansion in insulin resistant states. Pregnancy is a well-recognized physiological state of insulin resistance. Betatrophin levels in pregnant women and their relationships with metabolic variables remain to be elucidated. Methods A total of 49 pregnant women and 31 age-matched unpregnant women with normal glucose regulation (UP-NGR) were included. Among these subjects, according to results from 75 g oral glucose tolerance test (OGTT), 22 women were diagnosed as having gestational diabetes mellitus ( GDM ). Results Our study found that pregnant women, regardless of their glucose regulation status, had remarkably higher triglycerides (TG), total cholesterol (TC), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β). However, GDM patients had much lower HOMA-β compared with those of pregnant women with normal glucose regulation (P-NGR). Participants of the P-NGR group had almost 4 times higher levels of betatrophin than those of the UP-NGR group. Although betatrophin levels were lower in the GDM group than those of the P-NGR group, the difference did not reach statistical significance. Spearman correlation analysis showed that betatrophin levels were positively and significantly associated with total cholesterol, triglycerides, highdensity lipoprotein cholesterol (HDL-c), FINS and HOMA-β. However, adjustments of TC, TG and HDL-c eliminated the association between HOMA-β and betatrophin. Conclusions Pregnant women have significantly higher betatrophin levels in comparison to unpregnant women. Betatrophin levels are positively and significantly associated with β cell function and lipid levels. Furthermore, lipids may contribute to the association between betatrophin and β cell function.

Resumo Introdução Betatrofina tem sido relacionada à expansão de células β em estado de resistência à insulina. A gravidez é um conhecido estado fisiológico de resistência à insulina. Níveis de betatrofina em gestantes e sua relação com variáveis metabólicas ainda precisam ser esclarecidas. Métodos Um total de 49 gestantes e 31 não gestantes de mesma idade com níveis normais de glicose (UP-NGR) foram incluídas. Dentre elas, de acordo com os resultados da curva glicêmica, base em 75 g, 22 mulheres foram diagnosticadas com diabetes mellitus gestational ( DMG ). Resultados Nosso estudo identificou que gestantes, independente de seus níveis de glicose, tiveram notáveis níveis elevados de triglicerídeos (TG), colesterol (TC), insulina em jejum (FINS), HOMA-IR e HOMA-β. Contudo, pacientes com DMG tiveram bem menos HOMA-β se comparadas às gestantes com níveis normais de glicose ( P-NGR ). Participantes do grupo P-NGR tiveram níveis de betatrofina quase quarto vezes maiores ao das participantes do grupo UP-NGR. Embora os níveis de betatrofina sejam menores no grupo DMG do que no P-NGR, a diferença não obteve significância estatística. Análise da correlação de Spearman demonstrou que os níveis de betatrofina foram positiva e significativamente associados ao TC, TG, HDL-c (high-density lipoprotein cholesterol), FINS e HOMA-β. Contudo, ajustes em TC, TG e HDL-c eliminaram a associação entre HOMA-β e betatrofina. Conclusões Gestantes têm níveis de betatrofina significativamente maiores do que não gestantes. Níveis de betatrofina são positive e significativamente associados às células β funcionais e níveis de lipídeos. Além disso, lipídeos podem contribuir na associação entre betatrofina e células β funcionais.

Change of Serum Angiopoietin-related Growth Factor in Patients with Abdominal Aortic Aneurysm and Its Clinical Significance / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the changes and value of plasma angiopoietin-related growth factor (AGF) in patients with abdominal aortic aneurysm (AAA).</p><p><b>METHODS</b>Serum AGF level was analyzed in 50 AAA patients and in 56 healthy subjects. AGF and adiponectin were quantified by enzyme-linked immunosorbent assay. Routine testing of blood biochemistry and high-sensitivity C-reactive protein were performed.</p><p><b>RESULTS</b>The plasma AGF level was significantly higher in AAA patients than in the controls [(87.91±96.87) μg/L vs. (56.89±41.32) μg/L, P=0.040],while serum adiponectin level showed no significant difference between these two groups. The plasma AGF level in patients with an AAA>5 cm and those with AAA between 3 cm and 5 cm were (96.08±68.61) μg/L and (75.27±46.05) μg/L.</p><p><b>CONCLUSIONS</b>Plasma AGF is highly expressed in AAA patients. Higher serum AGF level is associates with larger AAA. Thus, AGF may be a potential serum biomarker for AAA.</p>

Elevated serum levels of betatrophin in patients with polycystic ovary syndrome and the influential factors / 中南大学学报(医学版)

OBJECTIVE@#To determine serum levels of betatrophin in patients with polycystic ovary syndrome (PCOS) and the influential factors. 
@*METHODS@#A total of 100 PCOS patients were enrolled randomly as a PCOS group, and 40 age-matched healthy women were recruited as a normal control (NC) group. Primary clinical or biochemical parameters of the subjects were detected. The results were analyzed by SPSS 19.0.
@*RESULTS@#Serum betatrophin levels were elevated in the PCOS group compared with the NC group. Serum betatrophin levels were positively correlated with age and Whole Body Insulin Sensitivity Index (WBISI),and negatively correlated with body mass index, fasting insulin(FINS), homeostatic model assessment insulin resistance (HOMA-IR) and homeostatic model assessment β cell function (HOMA-β). Multiple linear stepwise regression analysis showed that age and waist hip ratio (WHR) were independent influential factors for the level of betatrophin. PCOS was more likely to occur in women with higher betatrophin levels.
@*CONCLUSION@#Serum betatrophin levels increase in women with PCOS and they are independently associated with age and WHR. There is no significant correlation between betatrophin and insulin resistance or insulin levels.

Association between Maternal Serum Concentrations of Angiopoietin-like Protein 2 in Early Pregnancy and Subsequent Risk of Gestational Diabetes Mellitus / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A recent study reported a positive association between elevated serum levels of angiopoietin-like protein 2 (ANGPTL2) and the development of type 2 diabetes in a general population. However, the relationship of serum ANGPTL2 levels with the risk of developing gestational diabetes mellitus (GDM) has not been reported to date. The aim of this study was to investigate the change of maternal serum ANGPTL2 concentrations in the first trimester of pregnancy and to determine whether ANGPTL2 is a biomarker for subsequent GDM development.</p><p><b>METHODS</b>We conducted a prospective, nested case-control study in a pregnancy cohort. First-trimester ANGPTL2 levels were measured using a high-resolution assay in 89 women who subsequently developed GDM and in a random sample of 177 women who remained euglycemic throughout the pregnancy. Median ANGPTL2 levels were compared using Mann-Whitney U-test. Logistic regression was used to compute unadjusted and multivariable-adjusted odds ratios for developing GDM among ANGPTL2 quartiles.</p><p><b>RESULTS</b>The serum levels of ANGPTL2 was higher in women with GDM than that in women without GDM (3.06 [2.59, 3.65] ng/ml vs. 2.46 [2.05, 2.96] ng/ml, P = 0.003). Fasting blood glucose was higher in women with GDM than that in women without GDM (5.0 ± 0.9 mmol/L vs. 4.4 ± 0.6 mmol/L, P < 0.001). Glucose challenge test showed that the blood glucose was higher in women with GDM than that in women without GDM (9.1 ± 3.5 mmol/L vs. 6.2 ± 1.2 mmol/L, P < 0.001). A multivariate model adjusted for baseline characteristics, medical complications, and gestational characteristics revealed that the risk of developing GDM among women in Q4 compared with Q1 was 2.90-fold more likely to develop GDM later in pregnancy.</p><p><b>CONCLUSIONS</b>At 11-13 weeks in pregnancies that develop GDM, the serum concentration of ANGPTL2 is increased, and it can be combined with maternal factors to provide effective early screening for GDM.</p>

Dynamic roles of angiopoietin-like proteins 1, 2, 3, 4, 6 and 7 in the survival and enhancement of ex vivo expansion of bone-marrow hematopoietic stem cells

Recent advances in hematopoietic stem cells (HSCs) expansion by growth factors including angiopoietin-like proteins (Angptls) have opened up the possibility to use HSCs in regenerative medicine. However, the unavailability of true in vitro HSCs expansion by these growth factors has limited the understanding of the cellular and molecular mechanism of HSCs expansion. Here, we report the functional role of mouse Angptls 1, 2, 3, 4, 6 and 7 and growth factors SCF, TPO, IGF-2 and FGF-1 on purified mouse bone-marrow (BM) Lineage(-)Sca-1(+)(Lin-Sca-1(+)) HSCs. The recombinant retroviral transduced-CHO-S cells that secrete Angptls in serum-free medium were used alone or in combination with growth factors (SCF, TPO, IGF-2 and FGF-1). None of the Angptls stimulated HSC proliferation, enhanced or inhibited HSCs colony formation, but they did support the survival of HSCs. By contrast, any of the six Angptls together with saturating levels of growth factors dramatically stimulated a 3- to 4.5-fold net expansion of HSCs compared to stimulation with a combination of those growth factors alone. These findings lead to an understanding of the basic function of Angptls on signaling pathways for the survival as well as expansion of HSCs in the bone marrow niche.

Screening for new binding proteins which interact with BM2 of influenza B virus with yeast two-hybrid system / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the role of BM2 protein in the life cycle of influenza B virus.</p><p><b>METHODS</b>The authors screened human kidney MATCHMAKER cDNA library for new binding partners of BM2 of influenza B virus by using the yeast two hybrid system with truncated BM2 (26-109 aa) as the bait.</p><p><b>RESULTS</b>Six positive plasmids encoding N-acetylneuraminate pyruvate lyase, angiopoietin 3, zinc finger protein 251, ribosomal protein S20, protein arginine N-methyltransferase 1 variant 1 (PRMT) and transcription factor-like 1 (TCFL1) were obtained.</p><p><b>CONCLUSION</b>The results suggest that BM2 may play an important role in the life cycle of influenza B virus.</p>