Summary
This study investigated whether spontaneous lipid enrichment of human macrophages
affects their thrombogenic potential as measured by increased production of tissue
factor (TF) and plasminogen activation inhibitor types 1 and 2 (PAI-1 and PAI-2).
Macrophages were obtained following a 7-day culture period of monocytes, isolated
from the same donor, in autologous serum (HS) or in fetal bovine serum (FBS). Those
cultured in HS underwent marked lipid accumulation relative to those cultured in FBS
that was accompanied by increased production of TF and PAI-1, but not of PAI-2, and
decreased production of interleukin-1β. They also contained more arachidonic and linoleic
acid and lower amounts of n-3 polyunsaturated fatty acids, particularly docosahexaenoic
acid (22:6). These data indicate that the transformation of macrophages into foam
cells results in an increase in their thrombogenic and antifibrinolytic potential
and provide a possible explanation of the thrombotic sequelae frequently consequent
on plaque fissuring and disruption.