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 determi nants of transfer of low density lipoprotein (LDL) into the arterial w all, particularly in relation to the risk of development of atheroscle rosis. The flux of LDL into the arterial wall (in moles of LDL per sur face area per unit of lime) has two major determinants, i.e. the LDL c oncentration in plasma and the arterial wall permeability. LDL enters the arterial wall as intact particles by vesicular ferrying through en dothelial cells and/or by passive sieving through pores in or between endothelial cells. Estimates in vivo of the LDL permeability of a norm al arterial wall vary between 5 and 100 nl/cm(2)/h. In laboratory anim als, 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 expe rimental atherosclerosis. This supports the idea that an increased per meability to LDL, like an increased plasma LDL concentration, increase s the risk of atherosclerosis. Hypertension, smoking, genetic predispo sition, 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 ather osclerosis risk can be reduced by improving the barrier function of th e arterial wall towards the entry of LDL remains to be investigated; a gents which directly modulate the LDL permeability of the arterial wal l in vivo await identification.