Expression of platelet-activating factor receptor in human carotid atherosclerotic plaques - Relevance to progression of atherosclerosis

Background-Human monocyte-derived macrophages synthesize numerous proinflam matory and prothrombotic substances, including lipid mediators, such as pla telet-activating factor (PAF), which may play a major role in the onset and perpetuation of atherosclerotic lesions. In addition, both monocytes and m acrophages express PAF receptors (PAF-R). The expression of PAF-R is transc riptionally downregulated by oxidized LDL in in vitro primary cultures of m onocyte/macrophages. In this study, we evaluated the expression of PAF-R in human carotid plaque tissue, in foam cells isolated from human carotid pla ques, and in primary cultures of umbilical smooth muscle cells (SMCs). Methods and Results-We show that PAF-R was expressed at low levels in foam cells compared with monocyte/macrophages in plaques, as assessed by immunoh istochemical staining and in situ hybridization. In addition, low levels of mRNA were also detected by RT-PCR in isolated human carotid foam cells. A prominent finding of our study was the demonstration that contractile SMCs were positive for PAF-R, and its mRNA was extracted from primary cultures o f umbilical SMCs. Conclusions-As macrophages loose their inflammatory phenotype on transforma tion into foam cells, they may equally loose their capacity of defense agai nst aggression. We postulate that the diminished expression of PAF-R may be deleterious in the context of plaque formation and progression. The observ ation that arterial SMCs of contractile phenotype express PAF-R opens new a venues concerning the migration of these cells from media to intima and ath erosclerotic plaque formation.