Abstract
More than four decades ago it was established that an elevated low-density lipoprotein-cholesterol level was a risk for developing coronary artery disease. For the last two decades, statins have been the cornerstone of reducing low-density lipoprotein-cholesterol, but despite significant clinical efficacy in the majority of patients, a large number of patients suffer from side effects and cannot tolerate the required statin dose to reach their recommended low-density lipoprotein-cholesterol goals. Preliminary clinical studies indicate that monoclonal antibodies to PCSK9 appear to be highly efficacious in lowering low-density lipoprotein-cholesterol with a favourable adverse event profile. However, further longer-term clinical studies are required to determine their safety. From the early-proposed concept for high-density lipoprotein-mediated cholesterol efflux for the treatment of coronary artery disease, the concentration of the cholesterol content in high-density lipoprotein particles has been considered a surrogate measurement for the efficacy of the reverse cholesterol transport process. However, unlike the beneficial effects of the statins and monoclonal antibodies to PCSK9 in reducing low-density lipoprotein-cholesterol, no significant advances have been made to increase the levels of high-density lipoprotein-cholesterol. Here it is shown that by a non-pharmacological plasma delipidation means, the atherogenic low-density lipoproteins can be converted to anti-atherogenic particles and that the high-density lipoproteins are converted to particles with extreme high affinity to cause rapid regression of atherosclerosis.
Highlights
In 1976 it was first reported that a mixture of butanol and diisopropyl ether (DIPE) attained removal of triglycerides, free cholesterol (FC), EC, phospholipids, and unesterified fatty acids from plasma without protein denaturation
Lipids were removed from the delipidated plasma, all other constituents of plasma including the apolipoproteins remained intact, to the extent that delipidated plasma is used to measure apolipoproteins concentrations [7] [9]
The regressions of atherosclerosis not significant in the humans and monkeys, were similar to the results reported in apolipoprotein A1 (Apo A1) Milano studies [27]
Summary
Observations of Lipoproteins and Their Relationships with Atherosclerosis. More than 40 years ago, the Framingham Heart Study established that an elevated low-density lipoprotein-cholesterol (LDL-C) level was a risk for developing coronary artery disease (CAD) [1]. More than 40 years ago, Glomset [2] proposed that high-density lipoprotein (HDL) transfers cholesterol from peripheral tissues to the liver, where metabolites of the sterol are excreted into the bile. From the early proposed concept for HDL-mediated cholesterol efflux [3], the concentration of the cholesterol content in HDL particles has been considered a surrogate measurement for the efficiency of the reverse cholesterol transport (RCT) process. In the 1970s it was well established that plasma contained lipid carriers, some of which were detrimental to the body, LDLs, and others that were beneficial to the body, HDLs
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