허혈성 뇌졸중의 위험 인자로서의 아포지방단백 B/A1 비

함초롱,홍기숙 이화여자대학교 의과학연구소 2012 EMJ (Ewha medical journal) Vol.35 No.1

Objectives: According to current knowledge, apolipoprotein B/A1 (apoB/A1) ratio is like to be risk factor in coronary artery disease. There is evidence form case-control studies that apoB/A1 ratio may be a superior to LDL and HDL cholesterol in discriminating coronary artery disease case subject from control subject. However, relationship between apoB/A1 ratio and cerebral ischemic stroke is undefined. The main object of this study is to determine whether the risk of cerebral ischemic stroke is related to levels of apoB/A1. Methods: The study group included 643 patients (Men, 372; Women, 271) who diagnosed cerebral ischemic stroke between January 2008 to December 2010. The control groups were composed of 378 patients (Men, 139; Women, 239) who diagnosed other neurological disease. The correlation between lipid profiles and odds ratio of 10 preliminary risk factors (total cholesterol, triglyceride, LDL, HDL, apoA1, apoB, apoB/A1 ratio, non HDL, total cholesterol/HDL ratio, LDL/HDL ratio) for stroke were analyzed. Results: ApoB/A1 ratio was significantly increased in case patients compared with control subjects. Multivariate logistic regression analysis identified decrease of apoB/A1 ratio (odds ratio [OR], 1.583; 95% confidence intercal [CI], 1.105∼2.269) as significantly associated with stroke. Individual apoA1 (OR, 1.303; 95% CI, 0.967∼1.755) and apoB (OR, 1.397; 95% CI, 0.773∼2.523) were also not significantly associated with cerebral ischemic stroke. Conclusion: Increase of apoB/A1 ratio is associated with an increase risk of cerebral ischemic stroke. Use of apoB/A1 ratio is efficient as conventional lipids, for the identification of subjects at increased risk of stroke. So apoB/A1 ratio to standard lipid profile testing could improve the evaluation of risk factors of cerebral ischemic stroke.

Detecting the functional complexities between high-density lipoprotein mimetics

Sei, Yoshitaka J.,Ahn, Jungho,Kim, Taeyoung,Shin, Eunjung,Santiago-Lopez, Angel J.,Jang, Seung Soon,Jeon, Noo Li,Jang, Young C.,Kim, YongTae Elsevier 2018 Biomaterials Vol.170 No.-

<P><B>Abstract</B></P> <P>High-density lipoprotein (HDL) is a key regulator of lipid homeostasis through its native roles like reverse cholesterol transport. The reconstitution of this natural nanoparticle (NP) has become a nexus between nanomedicine and multi-disease therapies, for which a major portion of HDL functionality is attributed to its primary scaffolding protein, apolipoprotein A1 (apoA1). ApoA1-mimetic peptides were formulated as cost-effective alternatives to apoA1-based therapies; reverse-4F (r4F) is one such peptide used as part of a nanoparticle platform. While similarities between r4F- and apoA1-based HDL-mimetic nanoparticles have been identified, key functional differences native to HDL have remained undetected. In the present study, we executed a multidisciplinary approach to uncover these differences by exploring the form, function, and medical applicability of engineered HDL-mimetic NPs (eHNPs) made from r4F (eHNP-r4F) and from apoA1 (eHNP-A1). Comparative analyses of the eHNPs through computational molecular dynamics (MD), advanced microfluidic NP synthesis and screening technologies, and <I>in vivo</I> animal model studies extracted distinguishable eHNP characteristics: the eHNPs share identical structural and compositional characteristics with distinct differences in NP stability and organization; eHNP-A1 could more significantly stimulate anti-inflammatory responses characteristic of the scavenger receptor class B type 1 (SR-B1) mediated pathways; and eHNP-A1 could outperform eHNP-r4F in the delivery of a model hydrophobic drug to an <I>in vivo</I> tumor. The biomimetic microfluidic technologies and MD simulations uniquely enabled our comparative analysis through which we determined that while eHNP-r4F is a capable NP with properties mimicking natural eHNP-A1, challenges remain in reconstituting the full functionality of NPs naturally derived from humans.</P>

Association of Apolipoprotein B/Apolipoprotein A1 Ratio and Coronary Artery Stenosis and Plaques Detected by Multi-Detector Computed Tomography in Healthy Population

정창희,Jenie Yoonoo Hwang,신미선,유지희,김은희,배성진,양동현,강준원,박중열,이우제,김홍규 대한의학회 2013 Journal of Korean medical science Vol.28 No.5

Despite the noninvasiveness and accuracy of multidetector computed tomography (MDCT),its use as a routine screening tool for occult coronary atherosclerosis is unclear. We investigated whether the ratio of apolipoprotein B (apoB) to apolipoprotein A1 (apoA1), an indicator of the balance between atherogenic and atheroprotective cholesterol transport could predict occult coronary atherosclerosis detected by MDCT. We collected the data of 1,401 subjects (877 men and 524 women) who participated in a routine health screening examination of Asan Medical Center. Significant coronary artery stenosis defined as > 50% stenosis was detected in 114 subjects (8.1%). An increase in apoB/A1 quartiles was associated with increased percentages of subjects with significant coronary stenosis and noncalcified plaques (NCAP). After adjustment for confounding variables, each 0.1increase in serum apoB/A1 was significantly associated with increased odds ratios (ORs) for coronary stenosis and NCAP of 1.23 and 1.18, respectively. The optimal apoB/A1 ratio cut off value for MDCT detection of significant coronary stenosis was 0.58, which had a sensitivity of 70.2% and a specificity of 48.2% (area under the curve, 0.61; 95% CI, 0.58-0.63, P < 0.001). Our results indicate that apoB/A1 ratio is a good indicator of occult coronary atherosclerosis detected by coronary MDCT.

A simple electrochemical immunosensor platform for detection of Apolipoprotein A1 (Apo-A1) as a bladder cancer biomarker in urine

Kim, Seong-Eun,Kim, Young Joo,Song, Sunga,Lee, Kook-Nyung,Seong, Woo Kyeong Elsevier 2019 Sensors and actuators. B, Chemical Vol.278 No.-

<P><B>Abstract</B></P> <P>Bladder cancer is one of the tumors associated with the highest mortality rate. It is clinically characterized by high recurrent rates and poor prognosis once tumors invade the lamina propia. Nevertheless, current diagnostic techniques such as cystoscopy and cytology are invasive, time-consuming, and expensive. To address these challenges, we developed an electrochemical enzyme-linked immunosorbent assay (eELISA) platform on indium tin oxide (ITO) glass strips to quantify Apolipoprotein-A1 (Apo-A1) proteins in urine reported as an early bladder cancer biomarker with high sensitivity and specificity. We thoroughly studied the kinetics of ALP enzyme on the surface of ITO electrode so that we determined the minimum incubation time (2 min) and temperature (25 °C) for electrochemical measurement. Combined with chronocoulometry (CC) method under optimized conditions, our developed ITO-based eELISA platform can sensitively detect the existence of Apo-A1 as low as 1 pM in both PBS and urine with the dynamic range of concentrations (1 pM–100 nM) in a small one-drop assay system. Also, the simply prepared detection platform was successfully applied to urine condition. By using the developed platform, urine samples of bladder patients were clearly distinguished from normal controls. Our developed eELISA platform offers a simple and sensitive immunoassay approach for point-of-care (POC) diagnostic system.</P> <P><B>Highlights</B></P> <P> <UL> <LI> ITO-based eELISA monitors bladder cancer biomarkers with high sensitivity and reproducibility using urine samples. </LI> <LI> The immunosensor can sensitively detect the Apo-A1 as low as 1 pM in urine in a concentration range of 1 pM to 100 nM using only 15 ul of sample. </LI> <LI> The immunosensor strips are easy to handle and cost-effective for POC diagnostic system. </LI> </UL> </P>

Apolipoprotein A1 Inhibits TGF-β1-Induced Epithelial-to-Mesenchymal Transition of Alveolar Epithelial Cells

( Ae Rin Baek ),( Ji Min Lee ),( Hyun Jung Seo ),( Jong Sook Park ),( June Hyuk Lee ),( Sung Woo Park ),( An Soo Jang ),( Do Jin Kim ),( Eun Suk Koh ),( Soo Taek Uh ),( Yong Hoon Kim ),( Choon Sik Par 대한결핵 및 호흡기학회 2016 Tuberculosis and Respiratory Diseases Vol.79 No.3

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor β1 (TGF-β1).induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/ myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-β1.induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-β1 with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and α-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-β1 receptor type 1 (TβRI) and type 2 (TβRII) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-β1.treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-β1.induced change of the EMT phenotype. ApoA1 inhibited the TGF-β1.induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogenactivated protein kinase mediators. In addition, ApoA1 reduced the TGF-β1.induced increase in TβRI and TβRII expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-β1.induced EMT in experimental lung fibrosis.

中·高生에서의 血淸 脂蛋白値에 關한 硏究

독고영창,손창성,박종훈,이기형 고려대학교 의과대학 1995 고려대 의대 잡지 Vol.32 No.2

Lipoprotein(a) 〔Lp(a)〕 is a class of lipoprotein particles having the lipid composition of plasma low density lipoprotein(LDL), but with a distinct protein moiety composed of two proteins linked together by a disulfide bridge. The two proteins are apo B-100, the protein moiety of LDL, and apo(a), a heavily glycosylated protein that is specific for Lp(a). Apo(a) has a strong structural similarity to plasminogen and has a wide-size polymorphism that has a genetic origin and is partially responsible for the size and density heterogenecity of Lp(a). High plasma levels of Lp(a) are associated with a n incrased risk for cardiovascular disease that is related to atherogenic and thrombogenic potentials of this lipoprotein enhanced by the presence of other risk factors, among which are high plasma levels of LDL or low levels of high density lipoprotein. The factors determining of plasma levels of Lp(a) has not been clearly indentified. The study subjects were 86 boys and 80 girls aged 12 to 17 years. We measured serum concentration of Lp(a), apolipoprotein A-1 and B using the ELISA method. Median serum Lp(a) concentration was 12.0mg/dL, and median serum concentration of apolipoprotein A-1 and apolipoprotein B were 33.4mg/dL and 51.2mg/dL respectively. Girls had higher Lp(a) then boys(p<0.05), but sex-related differences were not, seen in apolipoprotein A-1 or apoprotein B. Age-related changes were not apparent for Lp(a) or apolipoprotein A-1 or apolipoprotein B. Lipoprotein Lp(a) apparently exerted atherogenic effects when it carried above 30mg/dL. In this study, above 30mg/dL of Lp(a) were 12(7.2%) subjects, who should be followed other cardiovascular risk factors and be treated. Lp(a) should be advised to correct to modifiable risk factors in order to decrease the cardiovascular pathogenecity of the lipoprotein class.

급성심근경색 및 당뇨병환자에서 혈청지질분획 및 Apolipoproteins

김신우,황종현,임현주,정의룡,류재근,채성철,전재은,박의현 慶北大學校 醫科大學 1994 慶北醫大誌 Vol.35 No.3

목적 : 동맥경화발생과 고지혈증과의 관계에 관한 연구로 최근에는 혈청지질의 분석외에 apolipoproteins에 관심이 증가되고 있지만 우리나라에서는 이 방면에 관한 연구가 별로 없는 상태이어서 본 연구를 하였다. 재료 및 방법 : 급성심근경색환자 31례와 성인병당뇨병환자 37례에서 몇가지 혈청지질과 apolipoprptein A1 및 B를 측정하여 건강인 36례의 성적과 비교, 검토하였다. 결과 : 1) 총 cholesterol, triglycerides, LDL-cholesterol 및 apolipoprptein B는 대조군에 비해 급성심근경색환자 및 당뇨병환자에서 유의하게 높았다. 2) HDL-cholesterol/총 cholesterol비 와 LDL-cholesterol/HDL-cholesterol비는 급성심근경색환자군에서만 각각 유의하게 감소 및 증가하였다. 총 cholesterol/Apo-B비와 Apo-A1/Apo-B비는 급성심근경색 및 당뇨병환자군 모두에서 대조군에 비해 유의하게 낮았다. 3) Apolipoprptein B는 총 cholesterol, triglycerides, LDL-cholesterol과 유의한 양의 상관이 있었으나 apolipoprptein A1은 그러하지 않았다. 4) 총 cholesterol이 200㎎/㎗미만인 급성심근경색환자에서는 대조군에 비해 여러지질치 가운데 apolipoprptein B만 유의하게 높았다. 결론 : 이상의 성적으로 보아 apolipoprptein B는 혈청지질중 특히 총 cholesterol, LDL-cholesterol과 유의한 상관이 있었으며 급성심근경색 및 당뇨병환자 모두에서 유의하게 높았다. In recent years, the studies of the relationship between coronary atherosclerosis and hyperlipidemia were focused upon analysis of apolipoproteins including serum lipids. However there were a few reports regarding to this field in Korea. We measered the levels of serum lipids and apolipoprotein A1 and B in 31 patients with acute myocardial infarction and 37 diabetics and compared the results with those in 36 healthy controls. The results were as follows'. Compared with the healthy controls, serum concentrations of total cholesterol, triglycerides, LDL-cholesterol and apolipoprotein B were significantly higher in patients with acute myocardial infarction and diabetics. Ratio of HDL-cholesterol/total cholesterol was significantly lower in pateints with acute myocardial infaction. Ratio of LDL-cholesterol/total cholesterol was significantly higher in patients with acute myocardial infarction. Patients with acute myocardial infarction and diabetics had a lower ratio of total cholesterol/Apo-B and Apo-A1/Apo-B. Level of apolipoprotein B was significantly higher in patients with acute myocardial infarction whose total cholesterol value were under 200 ㎎/㎗ than in controls. Apolipoprotein B was correlated significantly with LDL-cholesterol, total cholesterol and triglycerides but apolipoprotein A1 was not.

Ginsenoside-Rp1-induced apolipoprotein A-1 expression in the LoVo human colon cancer cell line

김미연,유병철,조재열 고려인삼학회 2014 Journal of Ginseng Research Vol.38 No.4

Background: Ginsenoside Rp1 (G-Rp1) is a novel ginsenoside derived from ginsenoside Rk1. This compoundwas reported to have anticancer, anti-platelet, and anti-inflammatory activities. In this study, weexamined the molecular target of the antiproliferative and proapoptotic activities of G-Rp1. Methods: To examine the effects of G-Rp1, cell proliferation assays, propidium iodine staining, proteomicanalysis by two-dimensional gel electrophoresis, immunoblotting analysis, and a knockdown strategywere used. Results: G-Rp1 dose-dependently suppressed the proliferation of colorectal cancer LoVo cells andincreased their apoptosis. G-Rp1 markedly upregulated the protein level of apolipoprotein (Apo)-A1 inLoVo, SNU-407, DLD-1, SNU-638, AGS, KPL-4, and SK-BR-3 cells. The knockdown of Apo-A1 by its smallinterferingRNA increased the levels of cleaved poly(ADP-ribose) polymerase and p53 and diminished theproliferation of LoVo cells. Conclusion: These results suggest that G-Rp1 may act as an anticancer agent by strongly inhibiting cellproliferation and enhancing apoptosis through upregulation of Apo-A1.

Apolipoprotein A1 Inhibits TGF-β1-Induced Epithelial-to-Mesenchymal Transition of Alveolar Epithelial Cells

Baek, Ae Rin,Lee, Ji Min,Seo, Hyun Jung,Park, Jong Sook,Lee, June Hyuk,Park, Sung Woo,Jang, An Soo,Kim, Do Jin,Koh, Eun Suk,Uh, Soo Taek,Kim, Yong Hoon,Park, Choon Sik The Korean Academy of Tuberculosis and Respiratory 2016 Tuberculosis and Respiratory Diseases Vol.79 No.3

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor ${\beta}1$ (TGF-${\beta}1$)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-${\beta}1$-induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-${\beta}1$ with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and ${\alpha}$-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-${\beta}1$ receptor type 1 ($T{\beta}RI$) and type 2 ($T{\beta}RII$) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-${\beta}1$-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-${\beta}1$-induced change of the EMT phenotype. ApoA1 inhibited the TGF-${\beta}1$-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-${\beta}1$-induced increase in $T{\beta}RI$ and $T{\beta}RII$ expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-${\beta}1$-induced EMT in experimental lung fibrosis.

Apolipoprotein A1 Inhibits TGF-β1–Induced Epithelial-to-Mesenchymal Transition of Alveolar Epithelial Cells

백애린,이지민,서현정,박종숙,이준혁,박성우,장안수,김도진,고은석,어수택,김용훈,박춘식 대한결핵및호흡기학회 2016 Tuberculosis and Respiratory Diseases Vol.79 No.3

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor β1 (TGF-β1)–induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/ myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-β1–induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-β1 with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and α-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-β1 receptor type 1 (TβRI) and type 2 (TβRII) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-β1–treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-β1–induced change of the EMT phenotype. ApoA1 inhibited the TGF-β1–induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogenactivated protein kinase mediators. In addition, ApoA1 reduced the TGF-β1–induced increase in TβRI and TβRII expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-β1–induced EMT in experimental lung fibrosis.