Angiopoietin-related Growth Factor Research Articles

Angiopoietin-like growth factor-derived peptides as biological activators of adipose-derived mesenchymal stromal cells

Adipose-derived mesenchymal stromal cells (AD-MSCs) are an essential issue in modern medicine. Extensive preclinical and clinical studies have shown that mesenchymal stromal/stem cells, including AD-MSCs, have specific properties (ability to differentiate into other cells, recruitment to the site of injury) of particular importance in the regenerative process. Ongoing research aims to elucidate factors supporting AD-MSC culture and differentiation in vitro. Angiopoietin-like proteins (ANGPTLs), known for their pleiotropic effects in lipid and glucose metabolism, may play a significant role in this context. Regeneration is a complex and dynamic process controlled by many factors. ANGPTL6 (Angiopoietin-related growth factor, AGF), among many activities modulated the biological activity of stem cells. This study examined the influence of synthesized AGF-derived peptides, designated as AGF9 and AGF27, on AD-MSCs. AGF9 and AGF27 enhanced the viability and migration of AD-MSCs and acted as a chemotactic factor for these cells. AGF9 stimulated chondrogenesis and lipid synthesis during AD-MSCs differentiation, influenced AD-MSCs cytokine secretion and modulated transcriptome for such basic cell activities as migration, transport of molecules, and apoptosis. The ability of AGF9 to modulate the biological activity of AD-MSCs warrants the consideration of this peptide a noteworthy therapeutic agent that deserves further investigation for applications in regenerative medicine.

Serum levels of angiopoietin-related growth factor in diabetes mellitus and chronic hemodialysis

Obesity is an increasing health problem all over the world. Angiopoietin-related growth factor (AGF, ANGPTL6) is a hepatocyte that directly regulates lipid, glucose and energy metabolism independent of angiogenic effects. In this study, we investigated circulating AGF levels in relation to kidney function, type 2 diabetes mellitus and insulin resistance. Angiopoietin-related growth factor was determined by enzyme-linked immunosorbent assay in subjects with a normal glomerular filtration rate (n = 44, 22 diabetic and 22 nondiabetic) and in patients on chronic hemodialysis (CD; n = 44, 22 diabetic and 22 nondiabetic). Median serum AGF levels were 176,6± 96,6 μg/L inpatients who underwent dialysis and 186,0±81,7 μg/L in patients not on dialysis. There was no statistically significant difference between the mean serum AGF levels of the patients who underwent dialysis and those who did not(p>0.05). AGF serum levels were significantly increased in diabetic patients (222,56±90,61 μg/L) as compared with non-diabetic patients (140,12 ± 66,06 μg/L) (P <0.05). In addition, we evaluated the relationship between biochemical parameters and anthropometric measurements of the patients and AGF in our study. BMI, HOMA, waist/hip circumference ratios positively correlated with circulating AGF in all patients. Our results suggest that T2DM is positively associated with AGF serum levels. We think that this study will be useful to explain the pathogenesis of AGF in insulin resistance. Further studies are needed to better elucidate the physiologic significance of circulating AGF in human.

Interplay between adipose tissue secreted proteins, eating behavior and obesity

PurposeAdipokines may play an important role in the complex etiology of human obesity and its metabolic complications. Here, we analyzed the relationship between 15 adipokines, eating behavior and body-mass index (BMI).MethodsThe study included 557 participants of the Sorbs (62.1% women, 37.9% men) and 3101 participants of the population-based LIFE-Adult cohorts (53.4% women, 46.4% men) who completed the German version of the Three-Factor-Eating Questionnaire to assess the eating behavior types cognitive restraint, disinhibition and hunger. Serum levels of 15 adipokines, including adiponectin, adipocyte fatty acid-binding protein (AFABP), angiopoietin-related growth factor (AGF), chemerin, fibroblast growth factor (FGF)-19, FGF-21, FGF-23, insulin-like growth factor (IGF)-1, interleukin (IL) 10, irisin, progranulin, vaspin, pro-neurotensin (pro-NT), pro-enkephalin (PENK) and leptin were measured. Based on significant correlations between several adipokines with different eating behavior items and BMI, we conducted mediation analyses, considering the eating behavior items as potential mediation variable towards BMI.ResultsHere, we found that the positive association between chemerin, AFABP or leptin and BMI in Sorbian women was mediated by higher restraint or disinhibited eating, respectively. Additionally, in Sorbian women, the negative relation between IGF-1 and BMI was mediated by higher disinhibition and the positive link between AGF and BMI by lower disinhibition. In Sorbian men, the negative relationship between PENK and BMI was mediated by lower disinhibition and hunger, whereas the negative relation between IGF-1 and BMI was mediated by higher hunger. In the LIFE-Adult women´s cohort, associations between chemerin and BMI were mediated by decreased hunger or disinhibition, respectively, whereas relations between PENK and BMI were fully mediated by decreased disinhibition.ConclusionOur study suggests that adipokines such as PENK, IGF-1, chemerin, AGF, AFABP and leptin might affect the development of obesity by directly modifying individual eating behavior. Given the observational nature of the study, future experimental or mechanistic work is warranted.

Multidimensional Biomarker Analysis Including Mitochondrial Stress Indicators for Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is accompanied by a complex and multifactorial pathogenesis with sequential progressions from inflammation to fibrosis and then to cancer. This heterogeneity interferes with the development of precise diagnostic and prognostic strategies for NAFLD. The current approach for the diagnosis of simple steatosis, steatohepatitis, and cirrhosis mainly consists of ultrasonography, magnetic resonance imaging, elastography, and various serological analyses. However, individual dry and wet biomarkers have limitations demanding an integrative approach for the assessment of disease progression. Here, we review diagnostic strategies for simple steatosis, steatohepatitis and hepatic fibrosis, followed by potential biomarkers associated with fat accumulation and mitochondrial stress. For mitochondrial stress indicators, we focused on fibroblast growth factor 21 (FGF21), growth differentiation factor 15 (GDF15), angiopoietin-related growth factor and mitochondrial-derived peptides. Each biomarker may not strongly indicate the severity of steatosis or steatohepatitis. Instead, multidimensional analysis of different groups of biomarkers based on pathogenic mechanisms may provide decisive diagnostic/prognostic information to develop a therapeutic plan for patients with NAFLD. For this purpose, mitochondrial stress indicators, such as FGF21 or GDF15, could be an important component in the multiplexed and contextual interpretation of NAFLD. Further validation of the integrative evaluation of mitochondrial stress indicators combined with other biomarkers is needed in the diagnosis/prognosis of NAFLD.

A vector-enzymatic DNA fragment amplification-expression technology for construction of artificial, concatemeric DNA, RNA and proteins for novel biomaterials, biomedical and industrial applications

A DNA fragment amplification/expression technology for the production of new generation biomaterials for scientific, industrial and biomedical applications is described. The technology enables the formation of artificial Open Reading Frames (ORFs) encoding concatemeric RNAs and proteins. It recruits the Type IIS SapI restriction endonuclease (REase) for an assembling of DNA fragments in an ordered head-to-tail-orientation. The technology employs a vector-enzymatic system, dedicated to the expression of newly formed, concatemeric ORFs from strong promoters. Four vector series were constructed to suit specialised needs. As a proof of concept, a model amplification of a 7-amino acid (aa) epitope from the S protein of HBV virus was performed, resulting in 500 copies of the epitope-coding DNA segment, consecutively linked and expressed in Escherichia coli (E. coli). Furthermore, a peptide with potential pro-regenerative properties (derived from an angiopoietin-related growth factor) was designed. Its aa sequence was back-translated, codon usage optimized and synthesized as a continuous ORF 10-mer. The 10-mer was cloned into the amplification vector, enabling the N-terminal fusion and multiplication of the encoded protein with MalE signal sequence. The obtained genes were expressed, and the proteins were purified. Conclusively, we show that the proteins are neither cytotoxic nor immunogenic and they have a very low allergic potential.

The association between dietary antioxidants and adipokines level among obese women

AimAdipokines are associated with several oxidative stress-related diseases and pathologic conditions. We aimed to assess the association between antioxidants and adipokines in obese adults. Methods and MaterialsIn this cross-sectional study, a total of 160 obese women were included. Body composition and anthropometric characteristics were measured. Dietary intakes were assessed by 3-day, 24-h dietary recall. Blood samples were obtained following an overnight fasting. Serum concentrations of adipokines including progranulin, retinol binding protein 4 (RBP4) and Angiopoietin-related growth factor 6 (ANGPTL6) was measured using an enzyme-linked immunosorbent assay. ANCOVA and the linear regression model analysis was performed to assess the relationship between Progranulin, RBP4, AnGPTL6, and antioxidants. ResultsMean age of included women was 39.31 ± 12.10. Mean and standard deviation for BMI was 35.05 ± 4.26 in this obese population. There was a positive significant association between ANGPTL6 and vitamin D intake (p < 0.001). Also, there was a marginal association between RBP4 and vitamin A (p = 0.063) intake, but after adjustment age, and fat mass, we found a significant association (p = 0.008). However, the associations between dietary antioxidants, progranulin, and ANGPTL6 were not statistically significant. ConclusionsANGPTL6 and RBP4 levels directly associated with dietary vitamins D and A intake, respectively. But, according to the results, the association between ANGPTL6 and vitamin D was bidirectional. The suggested associations probably can be useful in the development of interventional studies for management of chronic diseases.

Relationship Between 12 Adipocytokines and Distinct Components of the Metabolic Syndrome

Adipose tissue-derived signals potentially link obesity and adipose tissue dysfunction with metabolic and cardiovascular diseases. Although some adipocytokines have been closely related to metabolic and cardiovascular traits, it is unknown which adipocytokine or adipocytokine clusters serve as meaningful markers of metabolic syndrome (MS) components. Therefore, this study investigated the associations of 12 adipocytokines with components of the MS to identify the most relevant cytokines potentially related to specific metabolic profiles. Twelve cytokines [adiponectin, adipocyte fatty acid-binding protein (AFABP), angiopoietin-related growth factor, chemerin, fibroblast growth factor (FGF) 19, FGF21, FGF23, insulin-like growth factor-1, interleukin 10, irisin, progranulin, and vaspin] were quantified in a cross-sectional cohort of 1046 subjects. Hypothesis-free cluster analysis, multivariate regression analyses with parameters of the MS, and discriminant analysis were performed to assess associations and the relative importance of each cytokine for reflecting MS and its components. Among the studied adipocytokines, adiponectin, AFABP, chemerin, and FGF21 showed the strongest associations with MS and several MS components in discriminant analyses and multiple regression models. For certain metabolic components, these adipocytokines were better discriminators than routine metabolic markers. Other cytokines investigated in the present cohort are less able to distinguish between metabolically healthy and unhealthy subjects. Adiponectin, AFABP, chemerin, and FGF21 showed the strongest associations with MS components in a general population, suggesting that adverse adipose tissue function is a major contributor to these metabolic abnormalities. Future prospective studies should address the question whether these adipocytokines can predict the development of metabolic disease states.

Angiopoietin-related growth factor is independently associated with lower extremity peripheral arterial disease

AimsThe present study investigated the association of serum levels of angiopoietin-related growth factor (AGF) with lower extremity peripheral arterial disease (LEPAD). MethodsThe study group is comprised of 105 patients with lower extremity peripheral arterial disease. The control group consisted of 80 individuals without lower extremity peripheral arterial disease. Serum AGF concentrations were determined by enzyme-linked immunosorbent assay. The relationship between AGF and clinical and biochemical parameters was studied. Besides, this study analyzed AGF levels in LEPAD patients according to disease severity and evaluated the prognostic value of AGF for amputation and mortality in LEPAD patients after a follow-up period of 1.7years. ResultsMedian serum AGF levels were significantly higher in LEPAD group (103.70±64.69ng/mL) as compared with control group (53.83±37.87ng/mL) (P<0.001). In addition, T2DM patients with LEPAD exhibited markedly higher serum AGF concentrations (118.7±60.90ng/mL) than those without LEPAD (60.23±32.62ng/mL) (P<0.0001). Moreover, LEPAD positively predicted AGF concentrations in multivariate linear regression analysis (P<0.0001). Serum AGF levels were independently associated with LEPAD in binary logistic regression analysis model. Among LEPAD patients, those with critical limb ischemia (n=43) showed higher AGF levels (124.9±73.9 vs. 88.98±53.26ng/mL, P=0.01) compared with those with intermittent claudication (n=62). Furthermore, patients with the highest AGF tertile had an increased all-cause mortality and cardiovascular mortality (P=0.033 and P=0.025, respectively). ConclusionsOur results suggested that lower extremity peripheral artery disease was positively associated with AGF serum levels. High serum AGF level was a potential risk factor for LEPAD and associates with disease severity and poor outcome in LEPAD patients.

The suppression of hepatic glucose production improves metabolism and insulin sensitivity in subcutaneous adipose tissue in mice.

Despite the strong correlation between non-alcoholic fatty liver disease and insulin resistance, hepatic steatosis is associated with greater whole-body insulin sensitivity in several models. We previously reported that the inhibition of hepatic glucose production (HGP) protects against the development of obesity and diabetes despite severe steatosis, thanks to the secretion of specific hepatokines such as fibroblast growth factor 21 (FGF21) and angiopoietin-related growth factor. In this work, we focused on adipose tissue to assess whether liver metabolic fluxes might, by interorgan communication, control insulin signalling in lean animals. Insulin signalling was studied in the adipose tissue of mice lacking the catalytic subunit of glucose 6-phosphatase, the key enzyme in endogenous glucose production, in the liver (L-G6pc -/- mice). Morphological and metabolic changes in the adipose tissues were characterised by histological analyses, gene expression and protein content. Mice lacking HGP exhibited improved insulin sensitivity of the phosphoinositide 3-kinase/Akt pathway in the subcutaneous adipose tissue associated with a browning of adipocytes. The suppression of HGP increased FGF21 levels in lean animals, and increased FGF21 was responsible for the metabolic changes in the subcutaneous adipose tissue but not for its greater insulin sensitivity. The latter might be linked to an increase in the ratio of monounsaturated to saturated fatty acids released by the liver. Our work provides evidence that HGP controls subcutaneous adipose tissue browning and insulin sensitivity through two pathways: the release of beneficial hepatokines and changes in hepatic fatty acids profile.

Evaluation of cardiac risk marker levels in obese and non-obese patients with polycystic ovaries

Objective: To compare cardiac risk markers such as asymmetric dimethyl arginine (ADMA), C-reactive protein (CRP), homocystein (Hcy), plasminogen activator inhibitor-1 (PAI–1), vascular endothelial growth factor (VEGF), angiopoietin-related growth factor 6 (ANGPTL6) in obese and non-obese patients with polycystic ovary syndrome (PCOS).Study design: Thirty obese (BMI >30 kg/m2) and 30 non-obese (BMI < 30 kg/m2) patients diagnosed with PCOS and 30 age-matched healthy controls were included in the study. The ages of subjects were varying between 18 and 30 years. Serum ADMA, CRP, Hcy, PAI-1, VEGF and ANGPTL6 levels were analyzed for each subject.Results: Serum ADMA, CRP, Hcy, PAI-1, VEGF and ANGPTL6 levels were significantly elevated in obese and non-obese women with PCOS in comparison to control subjects (p < 0.05). This elevation was more obvious in the obese PCOS group than in the other group.Conclusions: Cardiovascular risk markers such as ADMA, CRP, Hcy, PAI-1, VEGF and ANGPTL6 levels are elevated in women with PCOS.

Hepatokines and non-alcoholic fatty liver disease

Nowadays non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver pathology both in adults and children. NAFLD manifestation ranges from a simple liver steatosis to steatohepatitis (nonalcoholic steatohepatitis – NASH), which may progress to advanced fibrosis, cirrhosis and end-stage liver disease. Due to the coexistence of visceral obesity, insulin resistance and dyslipidemia, NAFLD is considered to be the hepatic manifestation of metabolic syndrome. In recent years, in the pathogenesis of metabolic syndrome, type 2 diabetes mellitus, cardiovascular disease and also NAFLD, more and more attention has been paid to the so-called organokines, proteins with both paracrine or/ and endocrine activities. These include most known adipokines (mainly produced by adipose tissue), myokines (mainly produced by skeletal muscles) and hepatokines exclusively or predominantly produced by the liver. It was shown that the liver may affect the lipids and glucose metabolism by hepatokines released into the blood and NAFLD seems to be associated with altered hepatokines production. Fetuin-A, fibroblast growth factor-21 (FGF-21), selenoprotein P, sex hormone-binding globulin (SHBG), angiopoietin-related growth factor (also known as angiopoietin-related protein 6) and leukocyte derived chemotaxin 2 (LECT2) are considered as the most important hepatokines. In this review, we provide an overview of the main hepatokines and we summarize the association of liver-derived proteins with the development and progression of NAFLD.

Change of Serum Angiopoietin-related Growth Factor in Patients with Abdominal Aortic Aneurysm and Its Clinical Significance

To investigate the changes and value of plasma angiopoietin-related growth factor (AGF) in patients with abdominal aortic aneurysm (AAA). 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. 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. 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.

Hepatokines and non-alcoholic fatty liver disease.

Nowadays non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver pathology both in adults and children. NAFLD manifestation ranges from a simple liver steatosis to steatohepatitis (nonalcoholic steatohepatitis - NASH), which may progress to advanced fibrosis, cirrhosis and end-stage liver disease. Due to the coexistence of visceral obesity, insulin resistance and dyslipidemia, NAFLD is considered to be the hepatic manifestation of metabolic syndrome. In recent years, in the pathogenesis of metabolic syndrome, type 2 diabetes mellitus, cardiovascular disease and also NAFLD, more and more attention has been paid to the so-called organokines, proteins with both paracrine or/and endocrine activities. These include most known adipokines (mainly produced by adipose tissue), myokines (mainly produced by skeletal muscles) and hepatokines exclusively or predominantly produced by the liver. It was shown that the liver may affect the lipids and glucose metabolism by hepatokines released into the blood and NAFLD seems to be associated with altered hepatokines production. Fetuin-A, fibroblast growth factor-21 (FGF-21), selenoprotein P, sex hormone-binding globulin (SHBG), angiopoietin-related growth factor (also known as angiopoietin-related protein 6) and leukocyte derived chemotaxin 2 (LECT2) are considered as the most important hepatokines. In this review, we provide an overview of the main hepatokines and we summarize the association of liver-derived proteins with the development and progression of NAFLD.

Alterations of angiopoietin‐related growth factor (Angptl6) during pregnancy and in pre‐eclampsia

The aim of this study was to clarify the alterations of angiopoietin-related growth factor (AGF, also known as Angptl6/ARP5) in the serum of normally pregnant women and pre-eclamptic women and to explore the role of AGF in pre-eclampsia. Thirty healthy non-pregnant women, 118 normally pregnant women (30 at 6-12 gestational weeks, 30 at 13-28 weeks and 58 at 29-40 weeks, respectively) and 46 pre-eclamptic women were recruited. Fasting blood samples were obtained from all subjects. Fifteen women of healthy pregnant women provided their blood samples at 24 and 48 h after cesarean section, respectively. Enzyme-linked immunosorbent assay was used to determine the serum level of AGF. Serum levels of AGF were significantly higher in normally pregnant women than non-pregnant women (P < 0.001 of all). Although serum AGF of the first trimester was significantly higher than that of the second trimester (P = 0.033), there were no significant differences of serum AGF in the comparison between the first and third trimester (P = 0.064) and between the second and third trimester (P = 0.546). Serum AGF significantly decreased after delivery (P < 0.05). There were no significant differences in AGF of maternal serum between pre-eclamptic women and normally pregnant control women (P = 0.285). There were no significant differences in circulating AGF concentration between non-pregnant women and postpartum groups (P = 0.052 for 24 h after delivery and P = 0.083 for 48 h after delivery). The serum level of AGF was elevated in normal pregnancy compared with non-pregnant women, suggesting that placenta is an important source of circulating AGF during pregnancy.

Serum Levels of Angiopoietin-Related Growth Factor (AGF) Are Increased in Polycystic Ovary Syndrome

BackgroundPolycystic ovary syndrome (PCOS) is a frequent reproductive and metabolic disorder associated with insulin resistance. Recently, angiopoietins were identified in the systemic circulation and have been designated angiopoietinlike proteins (ANGPTL)....

Angiopoietin-related growth factor in the self-contained population of Sorbs

Angiopoietin-related growth factor in the self-contained population of Sorbs

Angiopoietin-related growth factor level in preeclampsia

Abstract Aim. Angiopoietin-related growth factor (AGF) is associated with angiogenesis but it can also affect glucose and energy metabolism. The aim of this study was to determine AGF levels in preeclampsia. Method. The study included 32 women with preeclampsia (preeclampsia group) and 32 non-preeclamptic, healthy, third trimester pregnant women (Control group). We analyzed serum levels of AGF and other biochemical and anthropometric markers in all subjects. Results. Serum AGF levels were significantly higher in subjects with preeclampsia (98.6 ng/mL) than those in the control group (52.2 ng/mL), (p-value<0.001). In preeclampsia group, mean sistolic blood pressure and mean diastolic blood pressure were found significantly higher than in control group (157.5 mm Hg/114.6 mm Hg, 100.9 mm Hg/70.0 mm Hg respectively). Also mean arterial pressure in preeclampsia group was significantly higher than in control group (119.7 mm Hg/84.8 mm Hg) (p-value<0.001). There was a significant positive association between AGF and systolic blood pressure, mean arterial pressure in preeclampsia group but there was no relationship between AGF and homeostasis model of assessment insulin resistance (HOMA-IR). Conclusion. Although systolic blood pressure can be a predictor of serum AGF level in preeclampsia, further studies are needed to explain the physiologic roles of AGF in physiopathology of preeclampsia. Keywords: Angiopoietin-related growth factor, preeclampsia Ozet Amac. Angiopoietin-iliskili buyume faktoru anjiogenez ile iliskilidir fakat glukoz ve enerji metabolizmasinida etkileyebilmektedir. Bu calismanin amaci preeklampside Angiopoietin-iliskili buyume faktorunun serum seviyelerinin belirlenmesidir. Yontem. Calisma 32 preeklampsili kadin (preeklampsi grubu) ve 32 saglikli 3. trimesterde gebe kadin (Kontrol grubu) ile yapildi. Tum olgularda, Angiopoietin-iliskili buyume faktorunun serum seviyeleri ile birlikte diger biyokimyasal ve antropometrik veriler analiz edildi. Bulgular. Preeklampsili olgularda Angiopoietin-iliskili buyume faktorunun serum seviyeleri (98,6ng/mL) kontrol grubundan (52,2 ng/mL) anlamli yuksekti (p-degeri<0,001). Preeklampsi grubunun ortalama sistolik kan basinci ve ortalama diastolic kan basinci degerleri kontrol grubundan anlamli yuksek bulundu (sirasiyla 157,5 mm Hg/114,6 mm Hg, 100,9 mm Hg/70,0 mm Hg). Ayrica, ortalama arteryel basinc da preeklampsi grubunda kontrol grubundan anlamli yuksekti (119,7 mm Hg/84,8 mm Hg) (p-degeri<0,001). Preeklampsi grubunda, Angiopoietin-iliskili buyume faktorun’un serum seviyeleri ile sistolik kan basinci ve ortalama arteryel basinc arasinda pozitif iliski tespit edildi ancak insulin direnci indeksi(HOMA-IR) ile iliski tespit edilmedi. Sonuc. Sistolik kan basinci, preeklampsili hastalarda serum Angiopoietin-iliskili buyume faktorun’un seviyeleri icin bir belirleyici olabilir ancak preeklampsinin fizyopatolojisinde Angiopoietin-iliskili buyume faktorun’un fizyolojik rolunun aciklanmasi icin baska calismalarada ihtiyac vardir. Anahtar soz cukler: Angiopoietin-iliskili buyume faktoru, preeklampsi

Angiopoietin-related growth factor level in preeclampsia

Angiopoietin-related growth factor level in preeclampsia

Targeted overexpression of Angptl6/angiopoietin‐related growth factor in the skin promotes angiogenesis and lymphatic vessel enlargement in response to ultraviolet B

Angiogenesis is required for physiological tissue repair processes, such as cutaneous wound healing. However, recent studies indicate that endogenous angiogenic factors may enhance photo-induced skin alterations in response to experimental ultraviolet (UV)-B exposure. Angiopoietin-related growth factor (AGF), also known as angiopoietin-like protein 6 (Angptl6), is known to promote new blood vessel formation and vascular hyperpermeability. Importantly, epidermal overexpression of Angptl6/AGF in mice promotes wound healing in the skin. However, it remains unclear whether overexpression of Angptl6/AGF facilitates tissue repair processes in response to UV-B irradiation. To test this hypothesis, we subjected Angptl6/AGF transgenic mice to acute or chronic UV-B exposure. Surprisingly, transgenic mice showed enhanced photosensitivity to subthreshold doses of UV-B that did not induce skin alterations in wild-type littermates. Marked enlargement of blood vessels was observed after a single exposure to UV-B in Angptl6/AGF transgenic mice, although no epidermal changes were observed. Chronic UV-B exposure over 14 weeks promoted cutaneous skin damage in Angptl6/AGF transgenic mice, whereas wild-type mice showed little or no macroscopic skin alteration. In addition to pronounced angiogenesis and epidermal hyperplasia, marked enlargement of dermal lymphatic vessels was observed in UV-B-exposed Angptl6/AGF transgenic mice. Electron microscopy analysis further revealed that the number and size of collagen bundles in the dermis was markedly reduced after chronic UV-B exposure in Angptl6/AGF transgenic mice. Taken together, these results indicate that ectopic expression of Angptl6/AGF in mice likely promotes UV-B-induced skin alterations, and that angiogenesis could be a therapeutic target in prevention of skin photo-aging.

Expression of angiopoietin-related growth factor in obese patients and its significance

Objective To investigate the expression of angiopoietin-related growth factor(AGF) in obese patients and its relationship with body mass index(BMI),waist circumference(WC),waist-hip ratio(WHR),blood glucose(FBG),plasma insulin(FINS) levels,and HOMA-insulin resistance index(HOMA-IR).Methods Plasma AGF levels were assayed by ELISA in 40 patients with obesity and 40 normal controls.The relationship of AGF level with BMI,WC,WHR,HbA1c,blood lipids,FBG,FINS,and HOMA-IR was also analyzed.Results AGF levels in patients with obesity were significantly increased compared with that in the control group([177.55 ± 74.09] ng/ml vs [122.37 ± 66.91] ng/ml,P 0.05).We also found that AGF level was positively correlated with Triglyceride(TG),FINS and HOMA-IR(r = 0.325,P 0.05;r = 0.451,P 0.01;r = 0.483,P 0.01);and was negatively correlated with high-density lipoprotein cholesterol(HDL,r =-0.529,P 0.01).Multiple regression analysis showed that HDL,BMI and FINS were the factors influencing AGF levels.Binomial Logistic regression analysis indicated that AGF level was positively correlated with obesity after adjusting sex,age,total cholesterol(TC),TG,HDL and low-density lipoprotein cholesterol(LDL)(OR 1).Conclusion The change of AGF level is associated with the metabolism disorder in obese patients,and it may also contribute to the pathogenesis of obesity.