|Support type:||Scholarships in Brazil - Master|
|Effective date (Start):||March 01, 2012|
|Effective date (End):||February 28, 2014|
|Field of knowledge:||Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology|
|Principal researcher:||Eliana Cotta de Faria|
|Home Institution:||Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil|
ABSTRACT Atherosclerosis is the leading cause of morbidity and mortality worldwide. It is estimated that there are about 200 million people with chronic or acute manifestations, and the reduction of plasma low-density lipoproteins (LDL) is the approach with greater effect on lowering mortality. High-density lipoprotein (HDL) acts preventing atherogenesis through several mechanisms. Niacin is a drug used to treat atherosclerosis, known to potentiate effects and increase HDL. Laropiprant minimizes the vasodilatory effects of niacin. This study aims to analyze the effects of niacin (1 a 2 g) with or without laropiprant on concentration, chemical composition, size and functionality of HDL and vascular actions in hypoalfalipoproteinemic individuals with or without hypertriglyceridemia. We will determine carotid artery intima-media thickness (IMT) and flow-mediated vasodilation (FMD) of brachial artery. Cholesterol (C), LDL-C, HDL-C and triglycerides will be measured by conventional enzymatic colorimetric methods. CETP activity will be measured through a radiometric test that measures the exogenous transfer of radioactive cholesteryl esters (CE) using plasma as a source of CETP. PLTP activity is measured using as substrate an exogenous radioactive emulsion. Apolipoproteins will be analysed by turbidimetric tests. Size distribution of particles will be analyzed by measurement using dynamic light scattering. As for the actions of HDL, antioxidant activity will be evaluated in vitro through the protective effect against LDL peroxidation, and the oxidation products formed will be analyzed quantitatively.For the anti-inflammatory activity of HDL, LDL is labeled with dichlorofluorescein (DCF). Fluorescence readings are taken in the SpectraMax M5/M5 Reader. Anti-apoptotic activity will be evaluated in cell culture tests with assessments by flow cytometry or fluorescence microscopy. Levels of nitrate / nitrite in the culture medium will be performed by the nitric oxide analyzer NOATM 280 and plasma oxidative stress will be estimated by plasma levels of 8-isoprostane. Parametric and nonparametric analysis will be made using the SAS programs and SPSS. We will associate the variables determining the effects of niacin combined or not with laropiprant on biochemical and vascular parameters.