Production of Platelet-Derived Growth Factor–like Mitogen by Smooth-Muscle Cells from Human Atheroma

Authors:
  • SWStephen J.C. Warner
    Stephen J.C. Warner
  • RSRobert N. Salomon
    Robert N. Salomon
  • LBLouis K. Birinyi
    Louis K. Birinyi
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Abstract
Proliferation of vascular smooth-muscle cells occurs during the development of atherosclerosis and the remodeling of arteries that accompanies chronic systemic or pulmonary hypertension. To help define the signals that initiate this abnormal growth, we cultured smooth-muscle cells from human atherosclerotic plaques. These cells (n = 9) released material into their culture medium that stimulated the proliferation of aortic smooth-muscle cells to a mean (±SD) level 5.1±1 times that in control medium. Part of this activity was due to molecules that resemble a mitogen first isolated from platelets and known as platelet-derived growth factor (PDGF), since these cells released PDGF measured in a radioreceptor assay (355±117 pg per milliliter per 48 hours; n = 6) and since anti-PDGF antibody neutralized 38±7 percent of this mitogenic activity (range, 13 to 60 percent; n = 6 carotid-plaque isolates). Two human genes encode distinct PDGF subunits that form dimers in different combinations to create biologically active PDGF. Cells cultured from human atheroma contained mRNAs for the PDGF A chain (16 of 17 isolates) but none (of 13) that encoded PDGF B chain (the c-sis protooncogene product).

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