When lowering plasma cholesterol, this does not affect cholesterol present in membranes

LDL particles in plasma are dedicated to transport cholesterol to peripheral tissues. LDL-c is secreted from the liver; the physiological pathway of clearing cholesterol from the body. About 80% of the LDL particles is removed through the LDL receptor and about 20% is removed through pathways independent of the LDL receptor. This 20% constitutes of the particles that can infiltrate the artery wall and produce atherosclerosis. Among the 80%, only one out of five particles will go to peripheral tissues. Thus, only part of the LDL-c serves a function in the periphery.

When patients are treated with lipid-lowering therapy, more particles will go to peripheral tissues and delivery of factors by LDL-c is not negatively impacted. Thus, if plasma LDL-c levels are lowered by means of increasing LDL-c clearance, this does not affect the cholesterol functions in the periphery.

Moreover, cells make their own LDL-c, independently of the plasma LDL-c level. Thus, cell function is not compromised at very low plasma LDL-c levels. This is confirmed by the observations that no health problems with regard to development, brain maturation, hormones and pregnancy are seen in patients with familial hypercholesterolemia who receive regular LDL-c apheresis.

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