SMOOTH-MUSCLE CELLS EXPRESS GRANULOCYTE-MACROPHAGE COLONY-STIMULATINGFACTOR IN THE UNDISEASED AND ATHEROSCLEROTIC HUMAN CORONARY-ARTERY

Granulocyte-macrophage colony-stimulating factor (GM-CSF), one of a fa mily of cytokines that regulate proliferation in macrophages and other types of cells, has been implicated in the inflammatory-fibroprolifer ative response of atherosclerosis. However, previous studies have been restricted to cultured cells and animal models. In the present study, we investigated GM-CSF expression in undiseased and atherosclerotic h uman coronary arteries at both the mRNA and protein levels. Dual in si tu hybridization/cell-marking experiments demonstrated that subpopulat ions of intimal smooth muscle cells (SMCs) and endothelial cells expre ss the cytokine in the histologically normal human coronary artery and that augmented expression occurs at these sites, and in macrophage ac cumulations and medial SMCs, in the atherosclerotic vessel. Correspond ing data were obtained by in situ hybridization and reverse transcript ion-polymerase chain reaction and Northern analyses of cultured cells. Cultured human coronary arterial SMCs showed constitutive expression of GM-CSF in cells that had adopted an activated synthetic phenotype. Electron microscope immunocytochemistry revealed that GM-CSF is a prot ein localized in the cytoplasmic matrix of SMCs of both the undiseased and atherosclerotic vessel wall; extracellular matrix was largely unl abeled, with only occasional small patches of amorphous immunopositive material. The expression of GM-CSF by subpopulations of intimal SMCs in the undiseased artery and the marked upregulation of GM-CSF apparen t in atherosclerotic lesions suggest roles for the cytokine in the cel lular events underlying initiation and progression of the human athero sclerotic lesion.