Transfer of low density lipoprotein into the arterial wall and risk of atherosclerosis.
The aim of the review is to summarize the present knowledge on determinants of transfer of low density lipoprotein (LDL) into the arterial wall, particularly in relation to the risk of development of atherosclerosis. The flux of LDL into the arterial wall (in moles of LDL per surface area per unit of time) has two major determinants, i.e. the LDL concentration in plasma and the arterial wall permeability. LDL enters the arterial wall as intact particles by vesicular ferrying through endothelial cells and/or by passive sieving through pores in or between endothelial cells. Estimates in vivo of the LDL permeability of a normal arterial wall vary between 5 and 100 nl/cm2/h. In laboratory animals, the regional variation in the arterial wall permeability predicts the pattern of subsequent dietary induced atherosclerosis. Moreover, mechanical or immunological injury of the arterial wall increases the LDL permeability and is accompanied by accelerated development of experimental atherosclerosis. This supports the idea that an increased permeability to LDL, like an increased plasma LDL concentration, increases the risk of atherosclerosis. Hypertension, smoking, genetic predisposition, atherosclerosis, and a small size of LDL may all increase the arterial wall permeability to LDL and in this way increase the risk of accelerated development of atherosclerosis. The hypothesis that atherosclerosis risk can be reduced by improving the barrier function of the arterial wall towards the entry of LDL remains to be investigated; agents which directly modulate the LDL permeability of the arterial wall in vivo await identification.
Nielsen
L B
LB
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Denmark. Lars_Bo_Nielsen@quickmail.ucsf.edu
D000818:Animals; D001158:Arteries / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism*; D001692:Biological Transport; D002463:Cell Membrane Permeability; D004705:Endocytosis; D004730:Endothelium, Vascular / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D000882:Haplorhini; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000493:pharmacokinetics; D008297:Male; D009994:Osmolar Concentration; D011817:Rabbits; D051381:Rats; D012307:Risk Factors
D008077:Lipoproteins, LDL