Observations on human smooth muscle cell cultures from hyperplastic lesions of prosthetic bypass grafts: Production of a platelet-derived growth factor—like mitogen and expression of a gene for a platelet-derived growth factor receptor—A preliminary study

• Published in: Journal of vascular surgery Vol. 10; no. 2; pp. 157 - 165
• Main Authors: Birinyi, Louis K., Warner, Stephen J.C., Salomon, Robert N., Callow, Allan D., Libby, Peter
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-08-1989; Elsevier
• Subjects: 550201 - Biochemistry- Tracer Techniques; ANIMAL CELLS; ANIMALS; BASIC BIOLOGICAL SCIENCES; Biological and medical sciences; Blood Vessel Prosthesis; BLOOD VESSELS; BODY; CARDIOVASCULAR SYSTEM; CATTLE; CELL CULTURES; Cell Division; CELL PROLIFERATION; Cells, Cultured; DOGS; DOMESTIC ANIMALS; GENE REGULATION; GENOTYPE; Graft Occlusion, Vascular - pathology; GRAFTS; GROWTH FACTORS; Humans; Hyperplasia; Immunoenzyme Techniques; IODINE ISOTOPES; Iodine Radioisotopes; ISOTOPE APPLICATIONS; ISOTOPES; MAMMALS; MAN; Medical sciences; MEMBRANE PROTEINS; MESSENGER-RNA; MITOGENS; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; MUSCLES; NUCLEIC ACIDS; ORGANIC COMPOUNDS; ORGANS; Platelet-Derived Growth Factor - analysis; Platelet-Derived Growth Factor - metabolism; PRIMATES; PROTEINS; RADIORECEPTOR ASSAY; RECEPTORS; Receptors, Cell Surface - genetics; Receptors, Platelet-Derived Growth Factor; RNA; RNA, Messenger - analysis; RNA, Messenger - isolation & purification; RUMINANTS; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; TRACER TECHNIQUES; TRANSPLANTS; Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels; VERTEBRATES; Human; Cell culture; Pathogenesis; Prosthesis; Hyperplasia; Cardiovascular disease; Smooth muscle; Artery; Northern blotting; Messenger RNA; Treatment; Bypass; Surgery; Complication; Platelet derived growth factor
• ISSN: 0741-5214; 1097-6809
• DOI: 10.1016/0741-5214(89)90349-2

Prosthetic bypass grafts placed to the distal lower extremity often fail because of an occlusive tissue response in the perianastomotic region. The origin of the cells that comprise this occlusive lesion and the causes of the cellular proliferation are not known. To increase our understanding of this process we cultured cells from hyperplastic lesions obtained from patients at the time of reexploration for lower extremity graft failure, and we studied their identity and growth factor production in tissue culture. These cultures contain cells that express muscle-specific actin isoforms, shown by immunohistochemical staining, consistent with vascular smooth muscle origin. These cultures also released material that stimulated smooth muscle cell growth. A portion of this activity was similar to platelet-derived growth factor, since preincubation with antibody-to-human platelet-derived growth factor partially blocked the mitogenic effect of medium conditioned by human anastomotic hyperplastic cells. These conditioned media also contained material that competed with platelet-derived growth factor for its receptor, as measured in a radioreceptor assay. Northern blot analysis showed that these cells contain messenger RNA that encodes the A chain but not the B chain of platelet-derived growth factor. In addition, these cells contain messenger RNA that encodes a platelet-derived growth factor receptor. We conclude that cultured smooth muscle cells from human anastomotic hyperplastic lesions express genes for platelet-derived growth factor A chain and a platelet-derived growth factor receptor and secrete biologically active molecules similar to platelet-derived growth factor. These data suggest that proliferating cells adjacent to failing arterial prostheses may stimulate their own proliferation by secreting and responding to platelet-derived growth factor—like mitogens, an autostimulatory or autocrine growth effect. The elaboration of smooth muscle mitogens by cells near the anastomotic sites of small-caliber prosthetic arterial bypass grafts may contribute to the failure that limits their clinical utility.