Arterial smooth muscle cells in primary culture produce a platelet-derived growth factor-like protein.

Abstract

Adult rat arterial smooth muscle cells (SMC) in primary culture modulate from contractile to synthetic phenotype. This process includes partial loss of myofilaments and formation of an extensive rough endpoplasmic reticulum and a large Golgi complex. It gives the cells the ability to initiate DNA synthesis and actively proliferate when stimulated with serum or isolated growth factors. After a few divisions, growth becomes partly independent of exogenous mitogens and does not cease until multiple cell layers were formed. Serum-free conditioned medium from primary cultures of adult rat arterial SMC contains a factor that initiates DNA synthesis in growth-arrested secondary cultures of SMC. The mitogenic activity was neutralized by antibodies to platelet-derived growth factor (PDGF), and no mitogenic activity occurred in conditioned medium from cultures pretreated with actinomycin D, exlcuding release into the medium of PDGF adsorbed to the plastic vessels during the initial culture in serum-containin medium. Exposure of human fibroblasts to samples of the conditoned medium at 4.degree. C inhibited subsequent binding of 125I-labeled PDGF. The SMC of the primary cultures were able to initiate DNA synthesis in a chemically defined medium lacking PDGF and other growth factors. During the early, most active, and partly autonomous growth phase, the SMC had a low binding capacity for 125I-labeled PDGF and responded but little to stimulation with exogenous PDGF. Taken together, the observations suggest that modulation of SMC from contractile to synthetic phenotype is accompanied by production ofa PDGF-like protein and autocrine or possibly by mitogen-independent initiation of DNA syntheiss. Functionally, this may be important during wound healing and in the development of atherosclerotic lesions.