Essential Role of Vascular Endothelial Growth Factor in Angiotensin II–Induced Vascular Inflammation and Remodeling

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2004-09, Vol.44 (3), p.264-270
• Main Authors: Zhao, Qingwei, Ishibashi, Minako, Hiasa, Ken-ichi, Tan, Chunyan, Takeshita, Akira, Egashira, Kensuke
• Format: Article
• Language: English
• Subjects: Angiotensin II - toxicity; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Animals; Aorta - pathology; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Cardiology. Vascular system; Cell Division; Chemokine CCL2 - biosynthesis; Chemokine CCL2 - genetics; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Coronary Vessels - pathology; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Extracellular Matrix Proteins - biosynthesis; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - physiology; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Genetic Therapy; Hypertrophy; Hypertrophy, Left Ventricular - etiology; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Imidazoles - pharmacology; Imidazoles - therapeutic use; Intercellular Adhesion Molecule-1 - biosynthesis; Intercellular Adhesion Molecule-1 - genetics; Interleukin-1 - biosynthesis; Interleukin-1 - genetics; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Macrophages - metabolism; Male; Medical sciences; Mice; Mice, Inbred C57BL; Myosin Heavy Chains; Natriuretic Peptide, Brain - biosynthesis; Natriuretic Peptide, Brain - genetics; Nonmuscle Myosin Type IIB; Nuclear Proteins - biosynthesis; Nuclear Proteins - genetics; Olmesartan Medoxomil; Receptors, CCR2; Receptors, Chemokine - biosynthesis; Receptors, Chemokine - genetics; Recombinant Fusion Proteins - physiology; Renin-Angiotensin System - physiology; Reverse Transcriptase Polymerase Chain Reaction; Tetrazoles - pharmacology; Tetrazoles - therapeutic use; Transcription Factors - biosynthesis; Transcription Factors - genetics; Transforming Growth Factor beta - biosynthesis; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta1; Tunica Media - drug effects; Tunica Media - pathology; Vascular Cell Adhesion Molecule-1 - biosynthesis; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - physiology; Vascular Endothelial Growth Factor Receptor-2 - biosynthesis; Vascular Endothelial Growth Factor Receptor-2 - genetics; Vasculitis - chemically induced; Vasculitis - physiopathology; Vasculitis - prevention & control; Ventricular Remodeling; Vertebrates: cardiovascular system
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.0000138688.78906.6b

Angiotensin II (Ang II) upregulates vascular endothelial growth factor (VEGF) and activates vascular inflammation. However, the decisive role of VEGF in Ang II–induced vascular inflammation and remodeling has not been addressed. Ang II infusion to wild-type mice increased local expression of VEGF and its receptors in cells of aortic wall and plasma VEGF, and caused aortic inflammation (monocyte infiltration) and remodeling (wall thickening and fibrosis). Hypoxia-inducible factor-1α colocalized with VEGF-positive cell types. Blockade of VEGF by the soluble VEGF receptor 1 (sFlt-1) gene transfer attenuated the Ang II–induced inflammation and remodeling. The sFlt-1 gene transfer also inhibited the increased expression of VEGF and inflammatory factors such as monocyte chemoattractant protein-1. In contrast, sFlt-1 gene transfer did not affect Ang II–induced arterial hypertension and cardiac hypertrophy. VEGF is an essential mediator in Ang II–induced vascular inflammation and structural changes through its proinflammatory actions.