Growth Factors Stimulate Neointimal Cells In Vitro and Increase the Thickness of the Neointima Formed at the Neck of Porcine Aneurysms Treated by Embolization

• Published in: Stroke (1970) Vol. 31; no. 2; pp. 498 - 507
• Main Authors: Desfaits, Anne-Cécile, Raymond, Jean
• Format: Journal Article
• Language: English
• Published: United States 01.02.2000
• Subjects: Aneurysm - pathology; Aneurysm - therapy; Animals; Anticoagulants - administration & dosage; Becaplermin; Carotid Arteries - pathology; Cell Division - drug effects; Dogs; Embolization, Therapeutic; Platelet-Derived Growth Factor - administration & dosage; Proto-Oncogene Proteins c-sis; Swine; Transforming Growth Factor beta - administration & dosage; Tunica Intima - pathology
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/01.STR.31.2.498

Background and Purpose —Growth factors (GFs) may favor the healing of aneurysms treated with endovascular techniques by stimulating neointima formation. Methods —Bilateral carotid aneurysms were constructed with venous pouches in 50 pigs and embolized intraoperatively with collagen sponges with and without GFs (platelet-derived growth factor-BB [PDGF-BB] 0.15 or 1.5 μg or transforming growth factor-β 1 [TGF-β 1 ] 60 or 600 ng) in each animal. DNA synthesis, cell proliferation, and collagen secretion assays were performed to assess the in vitro effects of GFs on neointimal cells harvested from the treated aneurysms. 125 I-PDGF-BB was used to study in vivo GF release from sponges. The thickness of the neointima at the surface of the sponges was measured 2 weeks after surgery. Since porcine aneurysms tend to heal after collagen sponge embolization, this experiment was repeated in dogs, which have shown a propensity for recurrence with the same technique, with 600 ng TGF-β 1 or platelet extracts. Results —PDGF-BB stimulated DNA synthesis and cell proliferation, while TGF-β 1 strongly increased collagen synthesis of neointimal cells in vitro. Clearance of 125 I-PDGF-BB from the sponges followed a biphasic curve, with 1.5% of exogenous PDGF-BB remaining at 1 week. The local delivery of PDGF-BB (0.15 or 1.5 μg) and TGF-β 1 (600 ng) significantly increased neointimal thickness at the neck of porcine aneurysms, while 60 ng of TGF-β 1 had no demonstrable effect. TGF-β 1 (600 ng) or platelet extracts had no influence on canine aneurysms. Conclusions —PDGF-BB and TGF-β 1 can stimulate neointimal cells in vitro and neointima formation in vivo, but TGF-β 1 and platelet extracts do not compensate for deficient thrombosis in canine aneurysms. Effects on the long-term results of embolization remain speculative.