The expression and clinical significance of LRP8 in colorectal cancer / 中国医师杂志

Objective:To investigate the expression of low density lipoprotein receptor associated protein 8 (LRP8) in colorectal cancer and its correlation with clinicopathological features.Methods:The surgical specimens of colorectal cancer patients hospitalized in Hunan Provincial People's Hospital from January 1, 2020 to September 1, 2020 (without adjuvant treatment measures such as radiotherapy, chemotherapy and immunotherapy) and 45 corresponding adjacent normal tissues were collected. Immunohistochemistry was used to detect the expression of LRP8 in colorectal cancer and paracancer normal tissues. The relationship between LRP8 and clinical characteristics of colorectal cancer patients was determined by univariate logistic regression analysis and Spearman correlation analysis.Results:Immunohistochemical results showed that LRP8 protein was highly expressed in 37 cases (82.22%) and low expressed in 8 cases (17.78%) of 45 colorectal cancer tissues. LRP8 protein was highly expressed in 17 cases (37.78%) and low expressed in 28 cases (62.22%). The expression of LRP8 protein in colorectal cancer tissues and adjacent normal tissues was significantly different ( P<0.05). Chi-square test showed that LRP8 protein expression was correlated with colorectal cancer stage, perineural invasion, vascular invasion, carcinoembryonic antigen (CEA) and low density lipoprotein (LDL) (all P<0.05), but not correlated with gender, age, tumor differentiation, Ki67, CA199, lymph node metastasis, triglyceride, total cholesterol and high density lipoprotein (all P>0.05). Logistic regression analysis showed that tumor node metastasis (TNM) stage, vascular invasion, nerve invasion, serum CEA and LDL levels were the influencing factors of LRP8 overexpression in patients with colorectal cancer (all P<0.05). There was a weak negative correlation between ApoB and tumor stage ( rs=-0.382), lymph node metastasis ( rs=-0.316) and vascular invasion ( rs=-0.311) (all P<0.05). Conclusions:Our results indicate that there is a higher expression of LRP8 in colorectal cancer tissues. The expression of LRP8 correlates with the staging of the colorectal cancer, neurovascular invasion, CEA, and low density lipoprotein. Patients with high expression of LRP8 have worse tumor stage and are more likely to have concurrent neurologic and vascular invasion.

Scavenger Receptor Class A to E Involved in Various Cancers / 전남의대학술지

Scavenger receptors typically bind to multiple ligands on a cell surface, including endogenous and modified host-derived molecules and microbial pathogens. They promote the elimination of degraded or harmful substances such as non-self or altered-self targets through endocytosis, phagocytosis, and adhesion. Currently, scavenger receptors are subdivided into eight classes based on several variations in their sequences due to alternative splicing. Since recent studies indicate targeting scavenger receptors has been involved in cancer prognosis and carcinogenesis, we will focus on the current knowledge about the emerging role of scavenger receptor classes A to E in cancer progression.

The role of lectin-like Ox-LDL receptor-1 on endothelial cell injury caused by human cytomegalovirus infection / 中华实验和临床病毒学杂志

Objective@#To investigate the role of lectin-like Ox-LDL receptor-1( LOX-1) in the activation and oxidative stress of cultured human umbilical vein endothelial cell(HUVEC) after human cytomegalovirus(HCMV) infection.@*Methods@#HUVEC were divided into four groups: HCMV, Control, Carrageenan, and HCMV+ Carrageenan. After HCMV AD169 infection, the supernatant of the culture was extracted, and cells were lysed. The levels of LOX-1 mRNA, intercellular adhesion molecule-1(ICAM-1) mRNA and vascular cellular adhesion molecule-1(VCAM-1) in HUVEC were measured by real-time PCR. And the content of nitrogen monoxidum(NO) of the supernatant was detected by nitrate reductase method accordingly.@*Results@#24 h after infection, the mRNA expression of LOX-1, ICAM-1 and VCAM-1 in HUVEC of HCMV infected group increased obviously compared to control, and NO quantity increased accordingly. The mRNA expression of LOX-1, ICAM-1 and VCAM-1 and the quantity of NO decreased after adding the LOX-1 inhibitor carrageenan. There was significant difference between groups(P<0.05).@*Conclusions@#HCMV may increase the mRNA expression of ICAM-1 and VCAM-1 and quantity of NO by upregulating the mRNA expresion of LOX-1, which may contribute to the formation of a therosclerosis(AS).

Effect of Lutein in the expression of PPAR? and LDLR in hypercholesterolemic male Wistar Rats

Background: Hyperlipidemia is a well known risk factor for cardiovascular disease, especially atherosclerotic coronary artery disease. Peroxisome proliferator activated receptor ? (PPAR?), a member of this nuclear receptor family, has emerged as an important player in this scenario, with evidence supporting a central co-ordinated role in the regulation of fatty acid oxidation, lipid and lipoprotein metabolism and inflammatory and vascular responses, all of which would be predicted to reduce atherosclerotic risk. The low-density lipoprotein (LDL) receptor (LDLR) is the primary pathway for removal of cholesterol from the circulation, and its activity is meticulously governed by intracellular cholesterol levels. Hence in this study we investigated the effect of Lutein on PPAR? and LDLR expression in liver of wistar rats.Methods: Male Wistar rats were divided into 6 groups of 6 each. Group I served as control. Group II III, IV, V and VI rats were received high cholesterol diet. Group III was treated with Atorvastatin 5mg/kg. Group IV, V and VI rats were treated with 25mg/kg, 50mg/kg and 100mg/kg of Lutein. After 16 weeks, liver tissue samples were collected from all the groups of animals to evaluate the expression of PPAR? and LDLR.Results: The expression of Peroxisome proliferator activated receptor ? and low-density lipoprotein (LDL) receptor (LDLR) was significantly increased in Lutein treated hypercholesterolemic male wistar rats.Conclusions: The results of this study indicate that Lutein activates LDL receptor and PPAR? in hypercholesterolemic male wistar rats.

Mechanism of Sclerostin/Lrp4 in the regulation of vascular smooth muscle cell calcification / 中华肾脏病杂志

Objective To investigate the possible mechanism of sclerostin/Lrp4 in calcification of VSMC induced by high phosphorus and the protective effect of Ginkgo biloba extract.Methods Aortic vascular smooth muscle cells (VSMCs) of SD rats were extracted and identified.VSMCs were divided into normal control group,high phosphorus induced calcification group (10 mmol/L β-glycerophosphate+50 μg/ml ascorbic acid),and high phosphorus induced calcification+Ginkgo biloba extract intervention group (10 mmol/L β-glycerophosphate+50 μg/ml ascorbic acid+0.5 mg/ml GBE),cultured in different mediums for 14 days.Vonkossa staining and alizarin red staining were used to detect the calcification of VSMCs.The mRNA level of BGP was detected by real time PCR,and the protein expressions of sclerostin and Lrp4 were detected by Western blot.Results Compared with normal control group,vonkossa staining and alizarin red staining showed significant calcium deposition in calcification group.Compared with calcification group,calcium salt deposition was significantly reduced in GBE treatment group.Real time PCR results showed β-catenin and BGP mRNA expressions in VSMC calcification group were higher than those in normal control group (P＜ 0.05).mRNA expressions of β-catenin and BGP in GBE treatment group were lower than those in calcification group (all P ＜ 0.05).Compared with normal control group,the protein expression of sclerostin was increased,but the protein expression of Lrp4 was decreased in calcified group (all P ＜ 0.05).Compared with calcification group,the protein expression of sclerostin decreased and the protein expression of Lrp4 increased in GBE treatment group (all P ＜ 0.05).Conclusions High phosphorus can induce VSMC calcification by activating Wn/β-catenin signaling pathway.Sclerostin/Lrp4 is involved in hyperphosphine-induced VSMC calcification.GBE can reduce the high phosphorus induced VSMC calcification by regulating the Wnt/β-catenin signaling pathway.

Adonesine A1 receptor and megalin defect in diabetic mice with early kidney disease / 中华肾脏病杂志

Objective To observe the effect of adenosine A1 receptor (A1AR) on the megalin defect in type 1 diabetic mice with early kidney disease.Methods 7-8 week-old,baseline body weight and fasting blood glucose matched wild type (WT) C57BL/6J mice were selected,and randomly divided into two groups:control group (n=6) and WT DM group (n=6).In the same way,male A1AR knock-out C57BL/6J mice were selected as A1AR-/-DM group (n=6).DM model was established by intraperitoneal injection of streptozocin.The blood glucose (BG),body weight (BW),kidney weight (KW),24 h proteinuria (24hUP) and albumin creatine ratio (ACR) were measured at 4 weeks.The renal pathological lesion was observed and the expression of megalin in proximal tubules was examined by immunohistochemistry.The expression of caspase-1,IL-18 and A1AR were detected by Western blotting.Results At 4th week,compared with WT control mice,the BG,BW,KW and 24hUP of WT DM mice were increased significantly (n=6,P ＜ 0.01),with the pathological glomerular enlargement,mesangial cell proliferation,extracellular matrix accumulation and renal tubule hypertrophy being observed.Immunohistochemistry revealed decreased expression of megalin,an important multiligand protein receptor on the brush border of proximal tubular epithelial cells in WT DM mice,which was correlated with 24hUP (r=-0.645,P ＜ 0.01).Compared with the control mice,the expressions of caspase-1,IL-18 and A1AR were significantly increased in WT DM mice (P ＜ 0.05).For A1AR-/-DM mice,more serious pathological lesion and megalin defect,together with increasing of casapase-1 and heavier proteinuria were observed than those in WT DM mice.Conclusion A1AR may play a protective role in megalin expression of diabetic mice with early kidney disease,in which the mechanism may be associated with caspase-1 related pyroptosis pathway.The details need further exploration.

Association of high-density lipoprotein and apolipoprotein E genetic variants with age-related macular degeneration / Associação de lipoproteína de alta densidade e variantes genéticas da apolipoproteína E com degeneração macular relacionada à idade

Purpose: This study aimed to evaluate the association of age-related macular degeneration (AMD) with apolipoprotein E (APOE) variants and serum lipid profiles, including levels and fractions of total serum cholesterol (TC), low-density lipoprotein cholesterol (LDLc), and high-density lipoprotein cholesterol (HDLc), and triglycerides (TG). Methods: Genotyping of APOE-HhaI was performed in 134 patients (study group, SG) and 164 individuals without AMD (control group, CG), aged 50-89 years. Lipid profiles were analyzed in a subgroup of 30 subjects of both groups, matched according to age and sex. The significance level was set at P<0.05. Results: APOE E3/E3 was more prevalent (SG=74.6%; CG=77.4%), with no difference between both groups (P=0.667). The same result was observed for risk genotypes (APOE E -/2: SG=7.4%; CG=10.3%, P=0.624). Serum levels of TC, LDLc, and TG revealed similar median values between SG (193.5, 116, and 155 mg/dL, respectively) and CG (207.5, 120, and 123.5 mg/dL, respectively; P >0.05). For HDLc, a higher median value was observed in SG (53.3 mg/dL) versus CG (42.5 mg/dL; P=0.016). Logistic regression analysis showed the same value, and the HDLc/TC ratio was -11.423 (P=0.014), as also confirmed by an increase in HDLc in SG. The association between lipid profiles and apolipoprotein E genotypes was similar in both groups (P>0.05). Conclusion: APOE-HhaI is not associated with AMD. However, an increase in serum HDLc level appears to exert a protective effect against the disease, irrespective of the genetic variants of apoE. .

Objetivo: Este estudo teve como objetivo avaliar a associação de degeneração macular relacionada à idade (DMRI) com variantes de alipoproteína E (APOE) e perfil lipídico sérico, incluindo níveis séricos de colesterol total (TC) e frações de proteínas relacionadas a receptor de LDL (LDLc) e HDL colesterol (HDLc), e triglicérides (TG). Métodos: Realizouse genotipagem de APOE-HhaI em 134 pacientes (grupo de estudo SG) e 164 indivíduos sem a doença (grupo controle CG), na faixa etária entre 5089 anos. O perfil lipídico sérico foi analisado em um subgrupo de 30 indivíduos de ambos os grupos, pareados por idade e sexo. Admitiuse nível de significância para valorP<0,05. Resultados: APOE E3/E3 prevaleceu (SG=74,6%; CG=77,4%), sem diferença entre os grupos (P=0,667), o mesmo ocorreu para genótipos de risco (APOE /E2: SG=7,4%; CG=10,3%,P=0,624).Níveis séricos de TC, LDLc e TG mostraram medianas semelhantes entre SG (193,5; 116; 155 mg/dL, respectivamente) e CG (207,5; 120; 123,5 mg/dL respectivamente; P>0,05). Para HDLc notouse valor de mediana elevado em SG (53,3 mg/dL) versus CG (42,5 mg/dL; P=0,016), constatado também na análise de regressão logística, cuja razão HDLc/TC mostrou coeficiente 11,423 (P=0,014), confirmando acréscimo de HDLc em SG. A relação entre perfil lipídico sérico e genótipos de APOE mostrou semelhança entre os grupos (P>0,05). Conclusão: APOE-HhaI não se associa a DMRI, no entanto, o acréscimo no nível sérico de HDLc parece ter efeito protetor contra a doença, independente de variantes genéticas da apoE. .

In silico Screening of Chemical Libraries to Develop Inhibitors That Hamper the Interaction of PCSK9 with the LDL Receptor

PURPOSE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low density lipoprotein receptor (LDLR) and promotes degradation of the LDLR. Inhibition of PCSK9 either by reducing its expression or by blocking its activity results in the upregulation of the LDLR and subsequently lowers the plasma concentration of LDL-cholesterol. As a modality to inhibit PCSK9 action, we searched the chemical library for small molecules that block the binding of PCSK9 to the LDLR. MATERIALS AND METHODS: We selected 100 chemicals that bind to PCSK9 where the EGF-AB fragment of the LDLR binds via in silico screening of the ChemBridge chemical library, using the computational GOLD algorithm analysis. Effects of chemicals were evaluated using the PCSK9-LDLR binding assay, immunoblot analysis, and the LDL-cholesterol uptake assay in vitro, as well as the fast performance liquid chromatography assay for plasma lipoproteins in vivo. RESULTS: A set of chemicals were found that decreased the binding of PCSK9 to the EGF-AB fragment of the LDLR in a dose-dependent manner. They also increased the amount of the LDLR significantly and subsequently increased the uptake of fluorescence-labeled LDL in HepG2 cells. Additionally, one particular molecule lowered the plasma concentration of total cholesterol and LDL-cholesterol significantly in wild-type mice, while such an effect was not observed in Pcsk9 knockout mice. CONCLUSION: Our findings strongly suggest that in silico screening of small molecules that inhibit the protein-protein interaction between PCSK9 and the LDLR is a potential modality for developing hypercholesterolemia therapeutics.

Role of leptin on the expression of low density lipoprotein receptor.

Background & objectives: Leptin resistance oriented hyperleptinaemia is a common problem in obese subjects in association with hypercholesterolaemia. The most common target for hypercholesterolaemia is impaired low density lipoprotein receptor (LDLR). This study was carried out to investigate whether any alteration in LDLR expression could explain the occurrence of hypercholesterolaemia in the event of hyperleptinaemia. Methods: Expression of LDLR and SREBP2 (sterol regulatory element binding protein 2) were examined in HepG2 cells by RT-PCR and Western blotting. JAK2 inhibitor II was used to verify the effect of JAK-STAT (Janus Kinase-Signal Transducer and Activator of Transcription) pathway (common mediator for cytokine signaling). Co-localization of LDLR and insulin receptor (IR) was examined by confocal microscopy. Results: Leptin was found to reduce the expression of LDLR and its transcription factor SREBP2. On the other hand, a weak signal for stimulation of LDLR by leptin was noted to be mediated by JAK2 pathway. But the joint effect of the two signaling pathways kept LDLR only in depressed mode in presence of leptin. Confocal microscopy showed that LDLR made an intensively co-localized complex with insulin receptor in presence of leptin. Interpretation & conclusions: Our results show that though leptin stimulates LDLR expression very weakly through JAK-STAT signaling pathway, it mainly imposes inhibition on LDLR expression by inhibiting transcription factor SREBP2. The inter-association between LDLR and IR may be a reason to render LDLR functionally inactive in presence of leptin.

Lectin-Like Oxidized LDL Receptor 1 Mediates the Uptake of the C-Terminal Domain of Hsp70 (A Promising Immune Adjuvant Molecule) and Antigen Peptide Complexes.

Extracellular heat shock protein 70 (Hsp70) is an adjuvant molecule that stimulates the immune system. The C-terminal domain of Hsp70 (C70), without the ATPase domain, is sufficient for antigen cross-presentation. However, the mechanism by which the receptor mediates the uptake of C70–peptide complex remains unclear. We therefore aimed to determine the process by which the receptor mediates the uptake of antigenic peptide-bound C70. Methodology: Hsp70 and C70 individually cloned into pET28a were expressed in Escherichia coli BL21 (DE3) and were purified on Ni-NTA agarose and MonoQ HR5/5. Hsp70 and C70 were labeled with Alexa 555 and Alexa 633, respectively, to detect cellular binding. HEK293 cells stably expressing lectin-like oxidized LDL receptor-1 (LOX 1) and KG-1 human dendritic-like cells were incubated with Alexa-labeled Hsp70 and C70 individually or with C70 and antigenic complexes and were observed using fluorescence microscopy. The affinity of LOX-1 toward Hsp70 and C70 was analyzed by chip assay using surface plasmon resonance, which immobilized LOX-1 ligand recognition domain. Results: HEK293 cells stably expressing LOX-1 and KG-1 cells accepted the C70– peptide and Hsp70–peptide complexes. Anti-LOX-1-neutralizing antibody inhibited the uptake of the C70–peptide complexes by KG-1 cells. The dissociation constant (KD) of C70 toward the LOX-1 extracellular domain, measured by surface plasmon resonance, was 4.02 × 10−7 M and that of the C70–peptide complex was 6.6 × 10−8 M. C70 increased the LOX-1 affinity by forming a complex with the antigen peptide. Conclusion: Our findings suggest that LOX-1 is the primary receptor for the C70–peptide and the Hsp70–peptide complexes. C70 is a promising adjuvant molecule that is internalized via LOX-1. In addition, it is convenient to prepare C70 using an E. coli expression system and C70 is more stable than full-length Hsp70.

Intertriginous Xanthoma in an Infant with Familial Hypercholesterolemia / 대한피부과학회지

Familial hypercholesterolemia is an autosomal dominant inherited metabolic disease characterized by high serum low-density lipoprotein (LDL) cholesterol concentrations, and xanthoma formation. There are multiple types of xanthomas, such as eruptive, tendinous, tuberous, and planar. Intertriginous xanthomas are rare, but, if present, are typically associated with familial homozygous hypercholesterolemia. We here report on a 15-month-old infant who presented with multiple yellowish linear patches and plaques on the intertriginous areas. Serum lipoprotein electrophoresis showed a marked increase in beta-fraction, suggesting type IIa hyperlipoproteinemia. Histopathology showed numerous aggregates of foam cells in the dermis. We performed DNA analysis and revealed the presence of an LDL receptor gene mutation. In summary, we here report an interesting case of an infant with intertriginous xanthoma. This condition is so rare that it has not been reported in the Korean dermatologic literature before.

Influence of anesthesia and surgery on the expression of transport receptors and catabolic enzymes of amyloid β-protein in aged rats / 解放军医学杂志

Objective: To investigate the expression changes in transport receptor and catabolic enzymes of amyloid β-protein (Aβ) in the brain of aged rats after surgery.

Expression of oxidized low density lipoprotein receptor-1 in aorta of diabetic rat and intervention of rosiglitazone / 中华老年医学杂志

Objective To observe the protein and mRNA expression of LOX-1,eNOS and PPARγ in type 2 diabetic rat aorta,and to investigate the effect of rosiglitazone intervention.Methods Totally 80 Wistar rats (7-week-old male) were randomized into the control group,high fat diet group,diabetic group,and rosiglitazone treatment group (n=20 each).Type 2 diabetes model was developed by intraperitoneal injection with a low dose of streptozotocin,and rats in rosiglization treatment group were treated with rosiglitazone by intragastric administration.After treatment with rosiglitazone for 6 and 12 weeks,animals were sacrificed.Aorta were collected for detecting the protein and mRNA expressions of LOX-1,eNOS and PPARγ,and the differences in expression levels were compared among groups.Results After 6 and 12 weeks,the protein expressions of LOX-1 were up-regulated in diabetic group and rosiglitazone treatment group as compared with control group and high fat diet group (all P＜ 0.01).The protein expression of LOX-1 was down-regulated in rosiglitazone treatment group as compared with diabetic group (P ＜ 0.05).The aorta protein expressions of LOX-1 in high diet group,diabetes group and rosiglitazone treatment group were upregulated after 12 weeks as compared with 6 weeks (all P＜0.01).After 6 and 12 weeks,the aorta protein expressions of eNOS were down-regulated and PPARγ were up-regulated in high fat diet group,diabetic group and rosiglitazone treatment group as compared with control group (all P＜0.01)The aorta protein expression of eNOS was down-regulated and PPARγwas up-regulated in diabetes group as compared with high fat diet group and rosiglitazone treatment group (all P＜0.01).The aorta protein expressions of eNOS in diabetes group and rosiglitazone treatment group were downregulated after 12 weeks as compared with 6 weeks (all P＜0.01).After 6 and 12 weeks,the aorta mRNA expressions of LOX-1 and PPARγ were up-regulated,but the mRNA expressions of eNOS were down-regulated in high fat diet group,diabetes group and rosiglitazone treatment group as compared with control group (all P＜0.05).The aorta mRNA expressions of LOX-1 and PPARγ were up-regulated,but the mRNA expressions of eNOS were down-regulated in diabetes group and rosiglitazone treatment group as compared with high fat diet group (all P＜0.05).The aorta mRNA expressions of LOX-1 and PPARγ were down-regulated,but the mRNA expressions of eNOS were upregulated in rosiglitazone treatment group as compared to diabetic group (all P＜0.01).Conclusions Both hyperglycemia and hyper-lipoproteinemia can induce early coronary atherosclerosis in rats with the abnormal protein and mRNA expressions of LOX-1,eNOS and PPARγ in rat aorta,and the abnormal expressions are more obvious in hyperglycemia combined with hyperlipoproteinemia.Thiazolidinediones can reverse the above abnormal expressions in diabetic rats.

Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy.

Effect of the Wnt/LRP5/β-catenin signaling pathway on the pathogenesis of postmenopausal osteoporosis / 中华妇产科杂志

Objective To investigate the role of the Wnt/LRPS/3-catenin signaling pathway in the pathogenesis of postmenopausal osteoporosis.Methods Fifty female Wistar rats aged 6-month-old,were randomly divided into control group ( NS,n =24 ) and ovariectomized group ( NOVX,n =26),NOVX underwent bilateral ovariectomy.At 0,4 and 8 weeks,all of rats were measured blood estrogen ( E2 ) and bone mineral density (BMD),4 and 8 weeks,low density lipoprotein receptor-related protein 5 (LRP5),3-catenin and Runx2 mRNA in bone were measured respectively by reverse transcription (RT)-PCR.Results In 4 and 8 weeks,compared with NS which had (117±29) and (114+15) pmol/L in E2 level,(0.098 ± 0.016 ) and (0.095 ± 0.028 ) g/cm2 in BMD,NOVX had significantly decreased to ( 92±15 ) and(95±22) pmol/L in E2 level ( P＜0.05 ),( 0.076 ± 0.016) and ( 0.052 ± 0.013 ) g/cm2 in BMD values ( P ＜ 0.01 ).And bone tissue LRP5,β-catenin and Runx2 mRNA expression was 1.02 ± 0.06,1.04 ±0.05,1.07 ±0.21 in NS,NOVX was significantly reduced to 0.97 ± 0.04,0.58 ± 0.05,0.86 ±0.03 (P＜0.05).Conclusion Wnt/LRP5/β-catenin signaling pathway may be important in the pathogenesis of postmenopausal osteoporosis.

Yellow wine and red wine inhibit matrix metalloproteinase-2 and improve pathological changes of atherosclerosis in LDL receptor knockout mice / 中国病理生理杂志

AIM: To study the possibility that yellow wine improves the pathological changes of atherosclerosis in vivo. METHODS: Six weeks old LDL receptor knockout mice (n=48) on a high-fat and L-methionine diet developed plasma hyperhomocysteinemia and atherosclerosis. The animals were randomly divided into yellow wine group, red wine group, ethanol group and control group (n=12 in each group) and were sacrificed after 14 weeks. The levels of plasma lipids and homocysteine in serum were examined. The morphological changes of aorta artery and the atherosclerosis of aorta sinus were observed under microscope. The expression and activation of matrix metalloproteinase-2 (MMP-2) were determined by the method of immunohistochemistry. RESULTS: No significant difference of plasma total cholesterol, triglyceride or high density lipoprotein cholesterol among groups was observed. Plasma homocysteine was significantly decreased in yellow wine group as compared to other three groups (P<0.01). Compared to ethanol and control groups, use of yellow wine and red wine significantly reduced the atherosclerosis lesion area (P<0.01). However, no significant discrepancy between the yellow wine group and red wine group was found. Compared to control group, the expression of MMP-2 in yellow wine group, red wine group and ethanol group decreased by 26.3%, 27.6% (P<0.01) and 5.7% (P>0.05), respectively. The activity of MMP-2 in yellow wine group, red wine group and ethanol group decreased by 31.7%, 32.5% (P<0.01) and 6.7% (P>0.05), respectively. CONCLUSION: Yellow wine and red wine inhibit the expression of MMP-2 and improve the pathologic changes of atherosclerosis, indicating that they have benefic effects on cardiovascular system.

Effects of APOE, APOB and LDLR variants on serum lipids and lack of association with xanthelasma in individuals from Southeastern Brazil

Xanthelasma might be a clinical manifestation of dyslipidemia, a recognized risk factor for coronary artery disease. We investigated the association of apolipoprotein E (APOE HhaI), apolipoprotein B (APOB XbaI and Ins/Del) and LDL receptor (LDLR AvaII and HincII) gene polymorphisms with lipid profiles in 100 Brazilians with xanthelasma and 100 controls. Allele frequencies were similar in both groups. APOE, APOB and LDLR genotypes were not correlated with differences in the serum lipid profile. In individuals with xanthelasma, the APOB D allele was associated with less chance of having increased LDL-cholesterol (O.R. = 0.16, CI95 percent = 0.03-0.94, p = 0.042). In the control group, the APOB X+ allele was associated with less chance of having both increased total cholesterol (O.R. = 0.16, CI95 percent = 0.03-0.78, p = 0.023) and increased LDL-cholesterol (O.R. = 0.10, CI95 percent = 0.02-0.60, p = 0.012). Moreover, there was a significantly higher frequency of control individuals (68 percent) with elevated serum triglyceride levels, compared to patients (48 percent, p = 0.008). On the other hand, triglyceride levels in controls also seemed to be influenced by all other gene polymorphisms studied, an effect that might be enhanced by environmental factors.

Impact of interleukin 1β on the expression of lectin-like oxidized LDL receptor 1 and ABCA1 in human mesangial cell line / 中华肾脏病杂志

Objective To observe the impact of IL-1β on the expression of lectin-like oxidized LDL receptor 1 (LOX-1) and ATP-binding cassette transporter A1 (ABCA1) in human mesangial cell line (HMCL), and its association with cholesterol homeostasis of HMCL. Methods Levels of LOX-1 and ABCA1 of HMCL induced by IL-1β were examined by using real-time PCR and Western blot. Results IL-1β up-regulated LOX-1 mRNA and protein expression. Treated with 5 μg/L IL-1β, the levels of LOX-1 mRNA and protein reached the peak after 6 h and 24 h of stimulation and were 6.87 folds and 1.88 folds of control rspectively. The expression of ABCA1 mRNA and protein of lipid-loaded HMCL was down-regulated by IL-1β Stimulated with 5 μg/L IL-1β the expression of ABCA1 mRNA and protein decreased to the lowest level, 19.0% and 50.62% of the baseline respectively. Conclusions The expression of LOX-1 can be up-regulated while the expression of ABCA1 can be decreased by the stimulation of IL-1β. IL-1β can enhance dyslipidemia and influence the balance of cholesterol homeostasis of HMCL.

Possible Implications of Placental Expressions for Heat Shock Protein 70 and Lectin-like Oxidized Low Density Lipoprotein Receptor-1 on Postnatal Blood Pressure in Their Newborns / 체질인류학회지

The 'fetal origin' hypothesis propose the alteration in fetal environment result in developmental adaptation, the permanently change in structure, physiology and metabolism, thereby predisposing to cardiovascular, metabolic and endocrine disease in adult life. Evidence is accumulating that the fetal environment affects newborn cardiac structure and function in humans, and blood pressure (BP) in newborn predicts the likelihood of developing hypertension in adult life. However, few studies have reported the influence of fetal factors on BP in neonates and an attempt to relate fetal factors to a neonate's BP seems to be important to identify individuals at risk of developing hypertension later in life. As the placenta is the regulator of nutrient composition and supply from mother to fetus and the source of hormonal signals that affect maternal and fetal metabolism, appropriate development of the placenta is crucial to normal fetal development. By virtue of these roles the placenta is in a key position to play a direct role in fetal programming. The aim of this study was to evaluate positive relationship between placental oxidative stress and BP in their healthy newborn offsprings, and propose to relate fetal factors to a neonatal BP. Systemic blood pressure was measured by automated device in 68 healthy term newborns who were born at Ewha Womans Medical Center, and their tissue samples of placentas were obtained from 40 cases which are 20 cases from high neonatal blood pressure group and 20 cases from low neonatal blood pressure group. We investigated placental expressions for heat shock protein (HSP) 70 and lectin-like oxidized low density lipoprotein receptor-1 (LOX-1), as markers for placental oxidative stress using immunohistochemistry and Western blot analysis, and evaluated their association with BP in healthy term newborn babies. The mean values of placental LOX-1 and HSP 70 were significantly higher in newborns with high BP group compared to those with low BP group. Increase in placental oxidative stress was associated with higher newborn systolic blood pressure. These findings suggest that newborn blood pressure may represent prenatal influence on cardiac structure and function.

DETECTING LOW DENSITY LIPOPROTEIN RECEPTOR MUTANT GENE OF RABBIT BY PCR / 药物分析学报

Objective Watanabe Heritable Hyperlipidaemic (WHHL) rabbits with low density lipoprotein receptor (LDLr) gene mutation have provided unprecedented opportunities for the study of human atherosclerosis, in order to confirm LDL receptor gene status in rabbits, we developed a simple PCR technique to detect LDL mutations in rabbits. Methods Rabbits genomic DNA were extracted from ear biopsy, and amplified by PCR to detect 12 bp deletion mutation in WHHL rabbits. PCR products were directly digested with BglⅠ, and then applied to polyacrylamide gel electrophoresis. Results PCR products from homozygous LDLr +/+ rabbits generated 2 bands of 212 and 94 bp after BglⅠ digestion, LDLr +/- rabbits generated 3 bands (294, 212, and 94 bp), LDLr -/- animals, however, generated only 1 product (294 bp). Conclusion This modified PCR method is simple and reliable.