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Published on: October 12, 2017
Comparative study of the activity and composition of HDL3 in Russian and American men
Y A Shakhov1, J F Oram, N V Perova
1Department of Medicine, University of Washington, Seattle 98195.
Insights
American high-density lipoprotein cholesterol (HDL) particles show greater protective function against heart disease than Russian HDL particles. This functional difference may explain higher coronary heart disease (CHD) risk in Russia.
Area of Science:
- Cardiovascular Research
- Lipid Metabolism
- Population Health
Background:
- Previous studies indicated a weaker inverse correlation between high-density lipoprotein cholesterol (HDL-C) and coronary heart disease (CHD) risk in Russian males compared to American males.
- It was hypothesized that HDL particles might offer less protection against CHD in Russian populations.
Purpose of the Study:
- To compare the functional activity and lipid composition of HDL3 particles from Russian and American men with varying HDL-C levels.
- To investigate potential reasons for observed differences in CHD risk between populations.
Main Methods:
- Isolation of HDL3 from blood plasma of men in Moscow and Seattle.
- Assessment of HDL3 functional activity in stimulating cholesterol efflux from fibroblasts.
- Measurement of HDL3's effect on cellular cholesterol esterification.
- Analysis of HDL3 binding to cell-surface sites and apolipoprotein E content.
Main Results:
- American HDL3 demonstrated higher activity in promoting cholesterol efflux and suppressing cellular cholesterol esterification compared to Russian HDL3, regardless of plasma HDL-C levels.
- These functional differences persisted even after removing apolipoprotein E-containing particles.
- While binding affinity to high-affinity sites was similar, Russian HDL3 exhibited higher non-specific binding.
Conclusions:
- This study reveals functional disparities between HDL particles from Russian and American populations for the first time.
- The reduced activity of Russian HDL3 in facilitating cholesterol efflux may contribute to the higher CHD risk observed in the Russian population.
Abstract:
Previous studies conducted within the framework of the Lipid Research Clinics Program showed a strong inverse correlation between high-density lipoprotein cholesterol (HDL-C) level and coronary heart disease (CHD) risk in American male populations, whereas in Russian populations such a correlation was less pronounced. It was assumed that HDL was less protective of CHD in Russian than in American males. This study compared the functional activity and lipid composition of HDL3 isolated from the blood plasma of men with low, normal, and high HDL-C levels from Moscow (Russia) and Seattle (United States) populations. Results obtained showed that American HDL3, irrespective of the plasma HDL-C level, had higher activity in stimulating both [3H]cholesterol and cholesterol mass efflux from cholesterol-loaded fibroblasts and in suppressing cellular cholesterol esterification when compared with Russian HDL3. American HDL3 remained more active than Russian HDL3, even when apolipoprotein E-containing particles were removed from HDL3 by heparin-Sepharose affinity chromatography. Russian and American 125I-HDL3 had similar binding to high-affinity cell-surface sites, but Russian HDL3 had a higher nonspecific binding component compared with American HDL3. This study demonstrates for the first time potential functional differences between HDL particles isolated from Russian and American populations. The lower activity of Russian HDL3 in promoting cellular cholesterol efflux may partly explain the higher CHD risk in the Russian population compared with the American one.
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