Objective
In view of the previously found discrepancy in relationship between high density lipoprotein (HDL) cholesterol (C) level and coronary heart disease (CHD) mortality in Russian men, and known HDL heterogeneity, the central hypothesis of this proposal is that HDL fractional distribution in Russian men which differ from that in US men, might be responsible for abnormalities in the functional activity of HDL particles which could be detected as cellular cholesterol efflux disorders. Biochemical, genetic and environmental factors, like pattern of alcohol consumption, might be responsible for abnormalities in HDL profile, found even in those with high HDL-C level.
This study will be conducted to evaluate the association of the compositional differences of HDL fractions with cellular cholesterol efflux from cultured cells with particular emphasis on the elucidating the possible reasons of discrepancies between relatively high HDL-C levels and high CHD risk in Russian men.
The specific aims are: to establish the extent to which sera from jects having relatively high or low HDL-C (either intrinsic or induced) vary in efflux potential; to establish correlations: between cellular cholesterol efflux and different blood lipoproteins (HDL, in particular) characteristics, and between the genetic polymorphism (if revealed) of major apolipoproteins and HDL functional activity assessed by HDL- mediated reverse cholesterol transport (RCT); to assess the association of rates and pattern of alcohol consumption with RCT parameters as possible specific environmental correlates of high HDL-C level.
The study will be performed in two steps: The comparative study of the cholesterol efflux potential of sera of Russian men differed by HDL-C level; The experimental interventional survey designed to reveal the association between moderate alcohol consumption (similar to Western pattern) and the cholesterol efflux potential of sera of Russian men differed by HDL-C level. jects (n=100, males, aged 40-59) with confirmed high (>50 mg/dl) or low (<40 mg/dl) HDL-C level will be included into the study; twenty jects will be selected to participate in 16-week-crossover study of "moderate alcohol intake.
Obtained data will permit to analyze the correlations between efflux ability of sera of Russian jects with low and high HDL- C level and those serum components which are the most probable factors affecting RCT activity, and to find the most important parameters, especially among HDL components, which might be responsible for disturbed HDL function even in those with elevated HDL-C level.
In other words, this study will probably reveal the most powerful and informative biochemical and/or genetic and/or environmental factors which level or distribution pattern could be assumed as markers of disturbed RCT.
Topic(s)
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59019 Lille
France