IDL, VLDL, chylomicrons and atherosclerosis
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In humans with the lipoprotein lipase deficiency disorder large amounts of chylomicrons and large very low-density lipoprotein (VLDL) accumulate in plasma. In spite of this, atherosclerosis does not seem to develop at an accelerated rate, suggesting that these lipoproteins do not promote atherogenesis. In humans with dysbetalipoproteinemia remnant lipoproteins (intermediate density lipoprotein (IDL) plus B-VLDL) accumulate in plasma and these particles may therefore be the factor causing accelerated atherosclerosis in this disorder.
Epidemiological studies in humans suggest that IDL or remnant lipoproteins are predictors of the severity or progression of atherosclerosis. Similar studies in the St. Thomas' Hospital rabbit strain, an animal model with genetically elevated plasma levels of VLDL, IDL and low-density lipoprotein (LDL), showed that IDL or remnant lipoproteins were better predictors of the extent of atherosclerosis than were LDL or VLDL.
Studies of lipoprotein/arterial wall interactions have demonstrated that the larger the lipoprotein particle, the lower the influx into intima. Very large VLDL and chylomicrons do not seem to enter intima. Although high-density lipoprotein (HDL) enters intima faster than other lipoproteins, the small HDL particles seem to penetrate the entire arterial wall and leave via lymphatics and vasa vasorum in the outer media and adventitia. In contrast, LDL, and possibly also IDL and smaller VLDL, may only leave the intima via the lumen of the artery.
In conclusion, a substantial body of evidence suggests that remnant lipoproteins (IDL and smaller VLDL) share with LDL the potential for promoting atherosclerosis, whereas very large VLDL and chylomicrons do not seem to have this effect.
Key wordsLipoprotein lipase deficiency Familial combined hyperlipidemia Dysbetalipoproteinemia The St. Thomas' Hospital rabbit strain Atherosclerosis Lipoprotein permeability
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