Hypercholesterolemia and, more specifically, high circulating levels of LDL-cholesterol have been linked to several important diseases in man. For this reason, a concerted effort is now underway to develop effective strategies to decrease the concentration of this lipoprotein in the plasma. Over the last few years, new advances have been made in our understanding of the factors that control the plasma LDL-cholesterol concentration. It is now possible to predict the changes that will occur in the plasma LDL-cholesterol concentration given any change in LDL receptor number or affinity or in the LDL-cholesterol production rate. From an analysis of these kinetic relationships several important conclusions emerge. First, in both man and the experimental animal the rate of LDL-cholesterol production is the most significant determinant of the plasma LDL-cholesterol concentration. Second, receptor-dependent LDL-cholesterol degradation accounts for the majority of total LDL-cholesterol degradation in all species studied. Third, in quantitative terms, receptor-dependent LDL-cholesterol degradation is restricted to the liver and, to a lesser extent, the small intestine. It is also clear that in order to significantly change the plasma LDL-cholesterol concentration by altering the rate of receptor-dependent LDL-cholesterol clearance, a change in receptor number, rather than receptor affinity, must be made since the system is resistant to even large variations in receptor affinity.


Cholesterol Permeability Lipase Triglyceride Hines 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • Jonathan B. Meddings
    • 1
  • John M. Dietschy
    • 1
  1. 1.Department of Internal MedicineUniversity of Texas Health Science Center at Dallas, Southwestern Medical SchoolHarry Hines Boulevard DallasUSA

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