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Background: Alopecia areata is a chronic inflammatory skin disease. Oxidative stress may contribute to the pathogenesis of this condition. Aim: To evaluate the serum oxidative stress markers and antioxidant capacity in patients with alopecia areata. Methods: This cross-sectional study was performed on 40 patients with alopecia areata and 40 healthy controls. The fasting blood sugar, C-reactive protein, lipid profile, and serum oxidative markers, including advanced glycation end products and advanced oxidation protein products, were measured in this study. Also, antioxidant enzymes, including paraoxonase-1, lecithin-cholesterol acyltransferase and serum ferric-reducing antioxidant power, were determined. Results: The serum levels of advanced glycation end products and advanced oxidation protein products were significantly higher in patients with alopecia areata, compared to the controls (P < 0.001), whereas the levels of ferric-reducing antioxidant power, paraoxonase-1 and lecithin-cholesterol acyltransferase were significantly lower in patients with alopecia areata, compared to the controls (P < 0.001). The mean fasting blood sugar level was significantly higher in patients with alopecia areata, compared to the controls. The ferric reducing antioxidant power level was significantly associated with the percentage of hair loss (P = 0.01, r = 0.4) and the serum C-reactive protein level (P = 0.03, r = –0.3) in patients with alopecia areata. Limitations: Since the current study had a cross-sectional design, no cause-effect relationship was established between alopecia areata and oxidative stress. The sample size of our study was also small. Conclusion: Based on the present results, the oxidant-antioxidant enzymatic system is impaired in alopecia areata due to the increased oxidative products and decreased antioxidant activity
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Lecithin-cholesterol acyltransferase deficiency is a rare genetic disease caused by a mutation of the gene coding for the lecithin-cholesterol acyltransferase protein, and mainly affects low density lipoprotein metabolism. It typically manifests with diffuse corneal opacities, normocytic anemia and kidney disease. We present the case of a 30-year-old man with chronic kidney disease and nephrotic syndrome. His initial kidney biopsy showed focal segmental glomerulosclerosis, thought to be primary, a disease which was refractory to multiple immunosuppressive schemes. Manifestations such as anemia, splenomegaly, corneal opacities and an association with low high-density lipoproteins alerted to the possibility of glomerular damage secondary to lecithin-cholesterol acyltransferase enzyme deficiency, which was confirmed through genetic sequenc ing. Due to the low incidence of the disease, diagnosis is a clinical challenge. The signs and symptoms tend to be interpreted as isolated events, which significantly delays its confirmation. Understanding this entity and the clinical exercise needed to arrive at its diagnosis will serve as a reference, resulting in the suspicion and reporting of cases in the future. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2558).
La deficiencia de lecitin-colesterol aciltransferasa es una enfermedad genética rara, causada por una mutación en el gen que codifica la proteína lecitin-colesterol aciltransferasa y afecta principalmente el metabolismo de las lipoproteínas de baja densidad. Se manifiesta típicamente con opacidades corneales difusas, anemia normocítica y enfermedad renal. Se presenta el caso de un hombre de 30 años con enfermedad renal crónica y síndrome nefrótico, con biopsia renal inicial que demostró un patrón de glomeruloesclerosis focal y segmentaria, interpretada como primaria, enfermedad que fue refractaria a múltiples esquemas de inmunosupresión. Las manifestaciones como anemia, esplenomegalia, opacidades corneales y la asociación con lipoproteínas de alta densidad bajas, alertaron sobre la posibilidad de compromiso glomerular secundario a un déficit de la enzima lecitin-colesterol aciltransferasa, confirmado mediante estudio de secuenciación genética. Dada la baja incidencia de la enfermedad, el diagnóstico representa un desafío clínico. Las manifestaciones suelen interpretarse como eventos aislados, lo que lleva a retraso significativo en su confirmación. El conocimiento de esta entidad y el ejercicio clínico necesario para llegar al diagnóstico, servirán como referencia que derive en la sospecha y reporte de futuros casos. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2558).
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Resumen Objetivo: determinar los valores séricos de la enzima lecitina colesterol aciltransferasa en un grupo de mujeres postmenopáusicas, y establecer su relación con factores asociados a riesgo cardiovascular. Materiales y métodos: estudio descriptivo transversal prospectivo, correlacional, que incluyó 56 mujeres postmenopáusicas en quienes se evaluaron variables antropométricas y bioquímicas (perfil lipídico y glicemia basal) asociadas a riesgo cardiovascular y se correlacionaron con las concentraciones séricas de lecitina colesterol aciltransferasa. Resultados: los valores séricos promedio de dicha enzima fueron 7,89 ± 1,26 (g/ml. Las mujeres con valores de índice de masa corporal superior a 25 tienen niveles séricos de lecitina colesterol aciltransferasa significativamente mayores que aquellas que tienen índice de masa corporal normal. No se observaron relaciones significativas entre los niveles de lecitina colesterol aciltransferasa y las variables bioquímicas evaluadas. Conclusiones: este trabajo es uno de los primeros que evalúa los niveles séricos de lecitina colesterol aciltransferasa en mujeres postmenopáusicas del Caribe colombiano. Se encontró una relación significativa entre los niveles séricos de lecitina colesterol aciltransferasa y los valores de índice de masa corporal elevados. Se requieren nuevos estudios para entender mejor la relación entre los niveles séricos de lecitina colesterol aciltransferasa y el riesgo cardiovascular en mujeres postmenopáusicas.
Abstract Objective: To determine the serum levels of lecithin cholesterol acyltransferase in a group of postmenopausal women and to establish their relationship with factors associated with cardiovascular risk. Materials and methods: A descriptive, correlational and cross-sectional study was performed that included 56 postmenopausal women. Anthropometric and biochemical (lipid profile and baseline blood glucose) variables associated with cardiovascular risk were measured, and were correlated with the serum concentrations of lecithin cholesterol acyltransferase. Results: The mean serum level of lecithin cholesterol acyltransferase was 7.89 ± 1.26 (g/ml. The women with a body mass index greater than 25 had significantly higher serum levels of the enzyme than those that had a normal body mass index. No significant relationships were observed between the levels of lecithin cholesterol acyltransferase and the biochemical variables evaluated. Conclusions: This study is one of the first that has evaluated the serum levels of lecithin cholesterol acyltransferase in postmenopausal women of the Colombian Caribbean. A significant relationship was found between the serum levels of lecithin cholesterol acyltransferase and elevated values of the body mass index. Further studies are required for a better understanding of the relationship between the serum levels of lecithin cholesterol acyltransferase and cardiovascular risk in postmenopausal women.
Subject(s)
Humans , Female , Middle Aged , Postmenopause , Heart Disease Risk Factors , Phosphatidylcholine-Sterol O-Acyltransferase , Arteriosclerosis , Cardiovascular Diseases , DyslipidemiasABSTRACT
The dietary fats are composed primarily of triacylglycerols and some amount of phospholipids and cholesterol. Being hydrophobic in nature, these are insoluble in water, and hence cannot be transported in the blood plasma per se; to enable these lipids to be transported by the blood stream to various peripheral tissues, nature has devised the technique of making these soluble by binding them to proteins. These proteins involved in lipid transport are known as apolipoproteins, and the protein-lipid particle is known as lipoprotein. Thus, lipoproteins can be considered to be the primary transportmechanism to carry lipids from the alimentary tract to various parts of the body. Lipoproteins have gained prominence in medical field over the past few decades because of their role in the aetio-pathogenesis of cardiovascular diseases, principally atherosclerosis which is the cause of coronary artery disease and myocardial infarction. The various types and sub-types of lipoproteins have been found to have differing and even opposing roles in the development of arterial diseases. An understanding of the differing populations of lipoproteins, the associated proteins and other enzymes, and the myriad variety of inter-actions among themselves and with body cells is vital to our understanding the pathways involved in the development of cardio-vascular disordersand in determining the precise steps where pharmacological interventions can be introduced
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Objective To develop a high-performance liquid chromatography (HPLC) method for the measurement of lecithin-cholesterol acyltransferase(LCAT) activity and analyze the relationships between LCAT activity and the traditional risk factors of atherosclerotic cardiovascular disease(CVD).Methods The liposome which contained 7-dehydrocholesterol and 1,2-didecanoyl-sn-glycero-3-phosphocholine (10∶0 PC)as the substrate of LCAT and LCAT activating peptide (LAP642)as LCAT activator was mixed with 10 microliters of serum sample(50∶ 1,V/V)in ice-water bath and subsequently incubated at 37 ℃ for 1 h.After extracting with hexane,the lipid was analyzed by HPLC and the LCAT activity was calculated as the ratio of 7-dehydrocholesterol ester to free 7-dehydroeholesterol.LCAT activities of 120 health volunteers were measured and its relationship with traditional risk factors of CVD was analyzed.Results The liposome composed of substrates(7-dehydrocholesterol and 10∶0 PC with ratio of amount 1∶ 8.5)and LAP642 was stable,efficient and easy for preparation.LCAT activity was a linear correction during 8 hours of incubation and was independent of the volume of serum added in the range from 0 to 20 microliters.The averages of intra-and total coefficients of variation(CV)were less than 1.76％ and 3.11％ respectively.The comparison of two methods showed that the results of the HPLC method were highly correlated with LCAT mass measured by commercial ELISA method and LCAT activity measured by endogenous substrate fractional esterification of high density lipoprotein cholesterol (FERHDL)(P ＜ 0.01).LCAT activity positively correlated with body mass index(BMI),triglyceride (TG) (P ＜ 0.05) and negatively correlated with apolipoprotein AI (apoAI) (P ＜ 0.05) and high density lipoprotein cholesterol (HDL-C) (P ＜ 0.01) in the volunteers.Conclusion A simple,precise and reliable HPLC method for determination of LCAT activity using artificial substrate has been established,and the results were not influenced by endogenous cholesterol levels in serum.The newly developed method could be a useful tool in the study of lipid metabolism and the assessment for risk factors of CVD.
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Epidemiological data clearly show the existence of a strong inverse correlation between plasma high-density lipoprotein cholesterol (HDL-C) concentrations and the incidence of coronary heart disease. This relation is explained by a number of atheroprotective properties of HDL, first of all the ability to promote macrophage cholesterol transport. HDL are highly heterogeneous and are continuously remodeled in plasma thanks to the action of a number of proteins and enzymes. Among them, lecithin:cholesterol acyltransferase (LCAT) plays a crucial role, being the only enzyme able to esterify cholesterol within lipoproteins. LCAT is synthetized by the liver and it has been thought to play a major role in reverse cholesterol transport and in atheroprotection. However, data from animal studies, as well as human studies, have shown contradictory results. Increased LCAT concentrations are associated with increased HDL-C levels but not necessarily with atheroprotection. On the other side, decreased LCAT concentration and activity are associated with decreased HDL-C levels but not with increased atherosclerosis. These contradictory results confirm that HDL-C levels per se do not represent the functionality of the HDL system.
Subject(s)
Animals , Humans , Atherosclerosis , Cholesterol , Coronary Disease , Incidence , Lecithins , Lipoproteins , Lipoproteins, HDL , Liver , Macrophages , Plasma , Sterol O-AcyltransferaseABSTRACT
The present study was carried out to explore the anti-diabetic, anti-dyslipoproteinemic and anti-oxidant activities of Anthocephalus indicus root extract in alloxan-induced (150 mg/kg body wt.) diabetic rats. A marked increase in plasma levels of glucose and lipid peroxides accompanied with an elevation in the lipids and apoprotein levels of serum very low density lipoprotein (VLDL) and low density lipoprotein (LDL) following decrease in lipid and protein constituents of high density lipoprotein (HDL) were observed. The alterations in lipoprotein pattern was associated with inhibition of lipolytic and antioxidant enzymes. Oral administration of root extract (500 mg/kg body wt.) for 30 days in dyslipidemic animals resulted in significant decrease in plasma glucose, total cholesterol, phospholipids, triglyceride and lipid peroxides. The decrease of lipids and apoprotein levels of VLDL and LDL were followed by stimulation of plasma post-heparin lipolytic activity and lecithin cholesterol acyltransferase as well as hepatic superoxide dismutase and catalase activities. Lipid and apoprotein levels of HDL were also recovered partially on treatment with root extract.
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Exogenous hypercholesterolemia in mice was induced by feeding with diets containing 2% cholesterol. It was found that Oil of Piper Longum Unsaponifiable Matter ( OPUM ) at 40mg/kg?d-1 ig for 20d could reduce the levels of total cholesterol (TC). ( LDL + VLDL) - c and the hepatic cholesterol content, increase that of biliary cholesterol in exogenous hypercholesterolemic mice. The hypocholesterolemic effect of OPUM is in a dose-dependent manner over the range of 20~40mg/kg. OPUM at 40mg/kg ig could elevate Lecithin - Cholesterol Acyltransferase ( LCAT ) activity inhibited by treating with ip of yolk. It was suggested that the hypochole-sterol effect of OPUM could be concerned with protectiong cholesterol esterification and be of great advantage to protection from arteriosclerosis arteriosclerosis in mice.