Heterogeneity of smooth muscle cells in advanced human atherosclerotic plaques: intimal smooth muscle cells expressing a fibroblast surface protein are highly activated by platelet-released products.
BACKGROUND
In vascular disease, smooth muscle cells (SMC) undergo phenotypic modulation and may acquire properties resembling those of fibroblasts in tissue wound healing.


OBJECTIVE
We aimed to show the differential expression of a fibroblast surface protein (FSP) by SMC in atherosclerotic lesions.


RESULTS
In early human coronary atherosclerotic lesions the expression of FSP in the intima was absent. In contrast, 29 of 29 middle/advanced lesions contained intimal SMC expressing high levels of FSP. Fibroblast surface protein positive SMC were negative for desmin but expressed variable levels of alpha-SM actin, SM caldesmon, SM myosin heavy chain and vimentin. Explants from advanced atherosclerotic lesions yielded two main SMC subpopulations. SMC over-expressing FSP exhibited higher in vitro mitogenic response (premitotic DNA synthesis) to sera (2- to 8-fold) and platelet-released products (8- to 26-fold), especially from thrombin-activated platelets, than FSP-negative SMC.


CONCLUSIONS
Our results suggest that the expression of FSP in SMC could indicate an activated phenotype, and the presence of highly positive FSP cells in the atherosclerotic lesions might be indicative of an increased SMC responsiveness to processes that locally generate thrombin and activate platelets.
Martínez-González
J
J
IIBB/CSIC-Institut de Recerca de l'Hospital de Sant Pau, Avda. Sant Antoni Maria Claret #167, 08025 Barcelona, Spain.
Berrozpe
M
M
Varela
O
O
Badimon
L
L
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology*; D001792:Blood Platelets / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology*; D003893:Desmin / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000071999:S100 Calcium-Binding Protein A4; D013917:Thrombin / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*
D002135:Calcium-Binding Proteins; D003893:Desmin; D007381:Intermediate Filament Proteins; D000071999:S100 Calcium-Binding Protein A4; C077591:S100A4 protein, human; D003094:Collagen; D013917:Thrombin; D013936:Thymidine