Blockade of vascular endothelial growth factor suppresses experimental restenosis after intraluminal injury by inhibiting recruitment of monocyte lineage cells

• Published in: Circulation (New York, N.Y.) N.Y.), 2004-10, Vol.110 (16), p.2444-2452
• Main Authors: OHTANI, Kisho, EGASHIRA, Kensuke, SATA, Masataka, SHIBUYA, Masabumi, SUNAGAWA, Kenji, HIASA, Ken-Ichi, QINGWEI ZHAO, KITAMOTO, Shiro, ISHIBASHI, Minako, USUI, Makoto, INOUE, Shujiro, YONEMITSU, Yoshikazu, SUEISHI, Katsuo
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Animals; Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Bone Marrow Transplantation; Cardiology. Vascular system; Carotid Artery Injuries - pathology; Carotid Artery Injuries - therapy; Catheterization - adverse effects; Cell Division; Cell Lineage; Constriction, Pathologic; Coronary heart disease; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endothelium, Vascular - physiology; Extracellular Matrix Proteins; Femoral Artery - injuries; Femoral Artery - pathology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Genetic Therapy; Genetic Vectors - pharmacology; Genetic Vectors - therapeutic use; Heart; Hyperplasia; Inflammation - prevention & control; Male; Medical sciences; Mice; Mice, Transgenic; Monocytes - pathology; Myosin Heavy Chains; Neovascularization, Physiologic; Nonmuscle Myosin Type IIB; Proteins - genetics; Proteins - physiology; Rabbits; Rats; Rats, Inbred WKY; Receptors, Vascular Endothelial Growth Factor - biosynthesis; Receptors, Vascular Endothelial Growth Factor - genetics; Recombinant Fusion Proteins - physiology; Recurrence; Regeneration; Solubility; Transduction, Genetic; Transfection; Tunica Intima - pathology; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - physiology; Vertebrates: cardiovascular system; Wound Healing - physiology
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.cir.0000145123.85083.66

Therapeutic angiogenesis by delivery of vascular endothelial growth factor (VEGF) has attracted attention. However, the role and function of VEGF in experimental restenosis (neointimal formation) after vascular intraluminal injury have not been addressed. We report herein that blockade of VEGF by soluble VEGF receptor 1 (sFlt-1) gene transfer attenuated neointimal formation after intraluminal injury in rabbits, rats, and mice. sFlt-1 gene transfer markedly attenuated the early vascular inflammation and proliferation and later neointimal formation. sFlt-1 gene transfer also inhibited increased expression of inflammatory factors such as monocyte chemoattractant protein-1 and VEGF. Intravascular VEGF gene transfer enhanced angiogenesis in the adventitia but did not reduce neointimal formation. Increased expression and activity of VEGF are essential in the development of experimental restenosis after intraluminal injury by recruiting monocyte-lineage cells.