Plasma kinetics of an LDL-like nanoemulsion and lipid transfer to HDL in subjects with glucose intolerance

OBJECTIVE: Glucose intolerance is frequently associated with an altered plasma lipid profile and increased cardiovascular disease risk. Nonetheless, lipid metabolism is scarcely studied in normolipidemic glucose-intolerant patients. The aim of this study was to investigate whether important lipid metabolic parameters, such as the kinetics of LDL free and esterified cholesterol and the transfer of lipids to HDL, are altered in glucose-intolerant patients with normal plasma lipids. METHODS: Fourteen glucose-intolerant patients and 15 control patients were studied; none of the patients had cardiovascular disease manifestations, and they were paired for age, sex, race and co-morbidities. A nanoemulsion resembling a LDL lipid composition (LDE) labeled with 14C-cholesteryl ester and ³H-free cholesterol was intravenously injected, and blood samples were collected over a 24-h period to determine the fractional clearance rate of the labels by compartmental analysis. The transfer of free and esterified cholesterol, triglycerides and phospholipids from the LDE to HDL was measured by the incubation of the LDE with plasma and radioactivity counting of the supernatant after chemical precipitation of non-HDL fractions. RESULTS: The levels of LDL, non-HDL and HDL cholesterol, triglycerides, apo A1 and apo B were equal in both groups. The 14C-esterified cholesterol fractional clearance rate was not different between glucose-intolerant and control patients, but the ³H-free-cholesterol fractional clearance rate was greater in glucose-intolerant patients than in control patients. The lipid transfer to HDL was equal in both groups. CONCLUSION: In these glucose-intolerant patients with normal plasma lipids, a faster removal of LDE free cholesterol was the only lipid metabolic alteration detected in our study. This finding suggests that the dissociation of free cholesterol from lipoprotein particles occurs in normolipidemic glucose intolerance and may participate in atherogenic signaling.

Metabolism of a lipid nanoemulsion resembling low-density lipoprotein in patients with grade III obesity

Introduction: Obesity increases triglyceride levels and decreases high-density lipoprotein concentrations in plasma. Artificial emulsions resembling lipidic plasma lipoprotein structures have been used to evaluate low-density lipoprotein metabolism. In grade III obesity, low density lipoprotein metabolism is poorly understood. Objective: To evaluate the kinetics with which a cholesterol-rich emulsion (called a low-density emulsion) binds to low-density lipoprotein receptors in a group of patients with grade III obesity by the fractional clearance rate. Methods: A low-density emulsion was labeled with [14C]-cholesterol ester and [³H]-triglycerides and injected intravenously into ten normolipidemic non-diabetic patients with grade III obesity [body mass index higher than 40 kg/m²] and into ten non-obese healthy controls. Blood samples were collected over 24 hours to determine the plasma decay curve and to calculate the fractional clearance rate. Results: There was no difference regarding plasma levels of total cholesterol or low-density lipoprotein cholesterol between the two groups. The fractional clearance rate of triglycerides was 0.086 ± 0.044 in the obese group and 0.122 ± 0.026 in the controls (p = 0.040), and the fractional clearance rate of cholesterol ester (h-1) was 0.052 ± 0.021 in the obese subjects and 0.058 ± 0.015 (p = 0.971) in the controls. Conclusion: Grade III obese subjects exhibited normal low-density lipoprotein removal from plasma as tested by the nanoemulsion method, but triglyceride removal was slower.

Avaliação do metabolismo de lipídes em diabéticos tipo 1, normolipidêmicos e sem complicações microvasculares e macrovasculares significativas através de nanoemulsão lipídica artificial / Evaluation of lipid metabolism in normolipidemic type 1 diabetes individuals without significant clinical microvascular and macrovascular complications through artificial lipid nanoemulsion

INTRODUÇÃO: portadores de diabetes mellitus tipo 1 (DM1) apresentam, progressivamente, complicações vásculo-neurais. Os fatores que aumentam o risco de coronariopatia - hipertensão, dislipidemia e idade avançada - explicam, em parte, a alta mortalidade cardiovascular, entretanto diabéticos tipo 1 podem morrer de coronariopatia precoce e não apresentar os fatores de risco clássicos para aterosclerose. Modificações estruturais e funcionais nas lipoproteínas, alterando a sua composição e trocas lipídicas poderiam justificar o aumento de eventos vasculares, entretanto estas alterações podem não ser detectadas através das dosagens rotineiras de lípides plasmáticos. OBJETIVOS: através de nanoemulsão lipídica artificial (LDE) que simula a estrutura lipídica da LDL avaliamos, em portadores de DM1, normolipidêmicos, intensivamente tratados e sem complicações significativas da doença, a taxa de esterificação do colesterol, a remoção da nanoemulsão da circulação, o tamanho da partícula HDL e as transferências de lípides entre a nanoemulsão e as partículas HDL. Secundariamente, determinamos a influência do controle glicêmico, resistência à insulina (RI) e insulinização no metabolismo lipídico. MÉTODOS: estudamos 36 indivíduos diabéticos e 37 controles não-diabéticos pareados para idade, sexo e índice de massa corpórea. Nanoemulsão lipídica artificial com marcação radioativa nos lípides éster de colesterol (CE), colesterol livre (CL), triglicérides (TG) e fosfolípides (PL) foi utilizada para os estudos. Nanoemulsão com marcação 14C-CE e 3H-CL foi injetada nos participantes e amostras de sangue foram coletadas durante 24 horas para mensuração da radioatividade. Remoção dos lípides da circulação foi calculada por análise compartimental. A taxa da esterificação do colesterol livre foi calculada após extração e separação de lípides do plasma por cromatografia em camada delgada. Para estudo da transferência de lípides, nanoemulsões com marcação 14C-CE e 3H-CL ou 14C-PL ...

INTRODUTION: people with type 1 diabetes mellitus (DM1) have progressively neuro-vascular complications. Factors that increase the risk of coronary artery disease hypertension, dislipidemia and advanced age explains part of increased cardiovascular mortality, however some DM1 died of early coronary artery disease and often do not have atherosclerosis classical risk factors. Structural and functional changes in lipoproteins, altering their composition and activities of lipid exchange could justify the increase in vascular events but these changes are generally not detected by routine clinical laboratory plasma lipid exams. OBJETIVES: in normolipidemic DM1, intensively treated and without significant complications of disease we evaluated, by an artificial lipid nanoemulsion that resembles the lipid structure of LDL, rates of cholesterol esterification, nanoemulsion removal of the circulation, HDL particle size and lipid transfer from nanoemulsion to HDL. Secondarily, we determine the influence of glycemic control, insulin resistance (IR) and insulinization on lipid metabolism. METHODS: we studied 36 diabetics and 37 non-diabetic controls paired by age, sex and body mass index. Artificial lipid nanoemulsion labeled with radioactive lipids cholesterol ester (CE), cholesterol (CL), phospholipids (PL) and triglycerides (TG) was used for studies. Intravenous infusion of nanoemulsion 14C-CE e 3H-CL was injected in participants and blood was sampled over 24 hours for radioactivity measurement. Circulation lipid removal was calculated through compartmental analysis. Rate of cholesterol esterification was calculated after lipid extraction and separation by thin-layer chromatography. Nanoemulsion was incubated with plasma and radioactivity of lipids 14C-EC, 3H-CL, 14C-PL and 3H-TG transferred to the HDL was quantified after the precipitation of other apoB lipoproteins. The HDL diameter was measured by laser light scattering. The insulin resistance in diabetic ...

Ateroesclerosis : ¿por qué una enfermedad inflamatoria?. Fundamentos, marcadores, biología molecular / Atherosclerosis : Why an inflammatory disease?. Basis, markers, molecular biology

En este artículo se resume brevemente el rol de la inflamación en la patogénesis y la fisiopatología de los síndromes coronarios agudos y los avances recientes del conocimiento sobre los factores responsables de la inestabilidad. Se examina la evidencia que sostiene la aseveración de que la inflamación de la placa ateroesclerótica puede jugar un rol clave en la patogénesis de la angina inestable y también los mecanismos a través de los cuales la activación de las células inflamatorias en la placa ateroesclerótica pueden conducir a una oclusión transitoria o permanente. El proceso de aterogénesis ha sido considerado fundamentalmente como la acumulación de lípidos dentro de la pared arterial; sin embargo es mucho más que eso. Las lesiones ateroescleróticas pueden describirse como correspondientes a una enfermedad inflamatoria. De hecho, la más precoz de las lesiones, la llamada estría grasa, es una lesión puramente inflamatoria, constituída sólo por macrófagos derivados de monocitos y linfocitos T. Se discute el uso de marcadores bioquímicos para la identificación y estratificación precoz de riesgo. La evaluación temprana del riesgo es esencial para la aplicación del tratamiento apropiado y el manejo futuro de pacientes con síndromes coronarios agudos. La proteína C reactiva, un reactante de fase aguda, es un marcador sensible de inflamación, y es un buen candidato para conocer el riesgo de futuros eventos cardiovasculares. La interacción adhesiva es un prerequisito para el normal funcionamiento de todos los componentes del sistema cardiovascular, sin embargo también está involucrada en la patogénesis de la enfermedad cardiovascular. Existe creciente evidencia de que las moléculas de adhesión (integrinas, selectinas y la superfamilia de las inmunoglobulinas) juegan un importante rol en la patología cardiovascular. Datos experimentales y epidemiológicos sugieren que la disyunción endotelial, luego de una infección o una inflamación, puede ser un factor de riesgo transitorio para enfermedad cardiovascular, que podría promover una respuesta vascular anormal. La disrupción, fisura o ruptura de placa, complican el curso de la ateroesclerosis coronaria. El riesgo de disrupción de una placa depende más de su composición que del tamaño de la placa y de la severidad de la estenosis...