Hypercholesterolemia cholesterol deposition

Familial hypercholesterolemia is characterized by a selective elevation in plasma LDL and deposition of LDL-derived cholesterol in tendons (xanthomas) and arteries (atheromas). 

The number of active LDL receptors is also affected by a condition called familial hypercholesterolemia, in which there is a defective gene coding for the receptor. In either case, the reduction of active receptors means that the LDL carrying cholesterol is unable to enter the cell interior instead, it is deposited in the arteries leading to the heart or brain. These deposits build up over time and may block blood supply to the heart muscle or brain, resulting in a heart attack or stroke. In contrast, HDL transports cholesterol from other parts of the body to the liver, where it is degraded to bile acids. 

Atherosclerosis and Plasma Lipids - Lipoprotein lipases play a critical role in the metabolism of lipoproteins and thus may be involved in athero-genesis. Hypercholesterolemia in the cholesterol-fed rabbit was attributed to the accumulation of chylomicron remnants, which may be formed on the aorta wall by lipoprotein lipase and deposited in the deep layers of the arterial wall without prior release into the blood stream.13 On this basis, cholesterol-rich lipoproteins in plasma may be the product rather than the cause of the atherogenic process. However, the defect in Type III hyperlipoproteinemia (broad- disease) may be ineffective removal of chylomicron remnant particles from the arterial wall,11 due to a failure of the liver to recognize such particles.15... 

Familial hypercholesterolemia is characterized by (1) a selective elevation in the plasma level of LDL, (2) deposition of LDL-derived cholesterol in tendons (xanthomas) and arteries (atheromas), and (3) inheritance as an autosomal dominant trait, with homozygotes affected more severely than heterozygotes. Homozygotes (prevalence 1 in 1 million) have severe hypercholesterolemia (650-1000 mg/dL), with the early appearance of cutaneous xanthomas and fatal CHD generally before age 20. The primary defect in familial hypercholesterolemia is the inability to bind LDL to the LDL receptor (LDL-R)... 

Macrophage yS-VLDL receptors may serve a back-up function in cholesterol clearance by facilitating removal of cholesterol-rich ]S-VLDL particles which accompany diet-induced hypercholesterolemia. When dog plasma cholesterol levels exceed 750 mg/dl, )8-VLDL accumulate in plasma and macrophages accumulate cholesterol and cholesterol esters [60]. The association of these events suggests that -VLDL may be taken up by macrophage j8-VLDL receptors for the deposition of plasma cholesterol esters. 

In a large population study Goldstein et al. discussed three frequent lipid disorders, familial hypercholesterolemia, familial hypertriglyceridemia, and familial combined hyperlipidemia. Ascorbate deficiency unmasks these underlying genetic defects and leads to an increased plasma concentration of lipids (e.g. cholesterol, triglycerides) and Hpoproteins (e.g. LDL, VLDL) as well as to their deposition in the impaired vascular wall. As with Lp(a), this deposition is a defense measure counteracting the increased permeability. It should, however, be noted that the deposition of lipoproteins other than Lp(a) is a less S[>ecific defense mechanism and fre-... 

A multitude of genetic defects lead to an increased synthesis and/or a decreased catabolism of cholesterol or LDL. A well characterized although rare defect is the LDL-receptordefect. Ascorbate deficiency unmasks these inherited metabolic defects and leads to an increased plasma concentration of cholesterol-rich lipoproteins, e.g. LDL, and their deposition in the vascular wall. Hypercholesterolemia increases the risk for premature CVD primarily when combined with elevated plasma levels of Lp(a) or triglycerides. 

Hood, B., and G. Angervall Studies in essential hypercholesterolemia and xanthomatosis. Belationship between age, sex, cholesterol concentrations in plasma fractions, and rise of tendinous deposits. Amer. J. Med. 26, 35 (1959). 

---