Recent information indicates that platelet-derived endothelial cell growth factor (PD-ECGF), a 45-kDa angiogenic protein, is expressed in the endothelium of various tissues and that its level of expression is correlated with the number of microvessels in human tumors. Because the formation of neovessels is also thought to play a role in atherosclerotic vascular remodeling, we analyzed PD-ECGF expression in fresh, coronary plaque tissues obtained by directional coronary atherectomy. Specimens from 31 patients were collected and analyzed by reverse transcription-polymerase chain reaction, histochemical staining, immunohistochemistry, and in situ hybridization with the use of PD-ECGF-specific primers and probes. Lesional vascular remodeling was assessed by intravascular ultrasound. PD-ECGF immunoreactivity and mRNA were found in plaque macrophages, endothelial cells of plaque neovessels, and stellate smooth muscle cells of 20 atherectomy specimens (64.5%). PD-ECGF immunoreactivity was correlated with the number of lesional microvessels and mast cells. Double-staining experiments revealed a close spatial proximity of PD-ECGF-positive cells and mast cells. Furthermore, the numbers of microvessels and mast cells were significantly higher in lesions lacking compensatory enlargement. The data indicate that PD-ECGF is expressed within cells of the atherosclerotic plaque and may be involved in driving angiogenesis in concert with mast cells.