The role of lipoproteins in atherogenesis.

Some of the concepts presented in this review can be recapped as follows: LDL is found in a much higher concentration in arterial intima than in any other connective tissue in the body. One response of the intimal to high LDL levels appears to be a toxic response resulting in atherosclerotic core formation, with eventual breakdown and rupture of the intima causing arterial thrombosis. The core does not develop simply from foam cell necrosis, but from a complex interaction of tissue lipoproteins, cells, and extracellular matrix. Core development is an early event in atherosclerosis progression, since the features of early cores can be found in lesions resembling fatty streaks. Lipoprotein aggregation and fusion may be key processes in extracellular lipid deposition. This is obviously an incomplete summary of the role of lipoproteins in atherosclerosis, but it does point toward new significant areas of research interest. There are several particularly intriguing research questions at the present time. How do the cholesterol-rich extracellular lipid deposits develop? Lipoprotein aggregation and fusion is a partial explanation, but how do deposits with 60% free cholesterol develop when the lipoproteins contributing to them have only 20-30% free cholesterol? Multiple hypotheses have been posed, but little evidence for any one pathway is available. Nevertheless, the extremely high levels of free cholesterol in the atherosclerotic core are likely to have effects on cellular membrane functions. Another intriguing question: How is core development related to the overall process of fatty streak to fibrous plaque conversion? The fibrous plaque has two hallmarks, one of which is a rather massive proliferation of cells and fibrous tissue, and the other is the development of the core. Our recent evidence suggests that core development may occur first (Guyton and Klemp, 1993).(ABSTRACT TRUNCATED AT 250 WORDS)