PubMed · 5241486
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L E Schaefer. 1968-03-26. Hyperlipidemia.. https://doi.org/10.1111/j.1749-6632.1968.tb27767.x
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This work studied the effect of cholesteryl hemisuccinate incorporation on membrane fluidity and on the kinetics of oxygen diffusion at different depths in the erythrocyte membrane. Cholesterol concentration in the membrane was expressed as the cholesterol-protein ratio (C/Pt). The membrane fluidity, as assessed by a fluorescence polarization method with diphenyl-hexatriene and 1-(4-trimethylamino)-6-phenylhexa-1,3,5-triene, decreased as the C/Pt ratio increased. Time-resolved fluorescence spectroscopy of pyrene dodecanoic acid (PDA) under an increasing C/Pt ratio in the erythrocyte membrane revealed enhanced oxygen diffusion in the middle of the membrane bilayer (in which PDA was incorporated), which was not the case with pyrene butyric acid (PBA) incorporated in the internal part of the membrane surface. It has generally been accepted that increased membrane fluidity reduces the physical barrier to oxygen permeation. Such conflicting observations on oxygen permeation in the rigidified erythrocyte membrane could be due to variations in oxygen solubility (preferential partitioning) in different polarity microdomains (cholesterol and phospholipid partitions).
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Growing evidence suggests that lowering serum cholesterol levels, particularly low-density lipoprotein levels, will reduce the risk for coronary heart disease. The benefit of cholesterol-lowering therapy has been documented by many clinical trials. Two secondary prevention trials, the Scandinavian Simvastatin Survival Study and the Cholesterol and Recurrent Events trial, demonstrated a striking reduction in recurrent coronary heart disease without an increase in noncardiovascular mortality; treatment with simvastatin reduced total mortality by 30 percent. A primary prevention trial, the West of Scotland Coronary Prevention Study, demonstrated similar results in high-risk patients without established coronary heart disease. More recent angiographic trials revealed that cholesterol-lowering therapy will reduce progression of atherosclerosis and, in some cases, will reverse existing lesions. Use of HMG-CoA reductase inhibitors also appears to be beneficial and safe. Evidence supports cholesterol-lowering therapy in high-risk patients, both with and without established atherosclerotic disease.