Atherosclerotic plaque growth

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Abstract
Focal smooth muscle cell proliferation is widely perceived as a key event in the formation of stenosing atherosclerotic lesions, but the stimuli for this remain uncertain. Soluble extracts of human aortic intima from proliferative gelatinous and transitional lesions, as well as surface encrusted thrombi, have been shown by us to be mitogenic for the chick chorioallantoic membrane (CAM). They have also been shown to stimulate increase in vascularity of the CAM. When active samples were passed through anti-albumin and anti-whole-serum affinity columns, mitogenic activity in the unabsorbed, fibrin related antigen fraction remained close to the original whole extract level. In contrast, when the unabsorbed fractions from anti-whole-serum columns were passed through an antifibrinogen affinity columns, the activity was reduced to insignificant levels. Similarly, whole extracts lost activity after passing through an antifibrinogen column. This has been taken one stage further by dividing the unabsorbed fraction from an anti-whole-serum column into two equal volumes and passing one half through an antifibrinogen fragment D affinity column, and the other through an antifibrinogen fragment E affinity column. The activity of the unabsorbed fraction from the fragment D column remained the same, but that from the fragment E column was significantly reduced. Most of the fibrin degradation products (FbDP) in lesion extracts are derived from fibrin, not fibrinogen, and clotting out fibrinogen and fragment X with thrombin did not remove the activity. Whole extracts of atherosclerotic lesions clotted on the CAM surface as has previously been shown with plasma. This suggests two pathways of activity, the immediate stimulation by preformed FbDP followed by that of FbDP released upon lysis of the clot. We conclude that such fibrin degradation products are a relevant source of mitogenic activity in human atherosclerosis

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