Essential role of vascular endothelial growth factor in angiotensin II-induced vascular inflammation and remodeling.
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-1alpha 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.
Zhao
Qingwei
Q
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Ishibashi
Minako
M
Hiasa
Ken-ichi
K
Tan
Chunyan
C
Takeshita
Akira
A
Egashira
Kensuke
K
D000804:Angiotensin II / Q000633:toxicity; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001011:Aorta / Q000473:pathology; D002455:Cell Division; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D003331:Coronary Vessels / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D020869:Gene Expression Profiling; D015316:Genetic Therapy; D006984:Hypertrophy; D017379:Hypertrophy, Left Ventricular / Q000209:etiology; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018995:Myosin Heavy Chains; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis / Q000235:genetics; D024501:Nonmuscle Myosin Type IIB; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D000068557:Olmesartan Medoxomil; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D053773:Transforming Growth Factor beta1; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000235:genetics; D014657:Vasculitis / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D020257:Ventricular Remodeling
D047228:Angiotensin II Type 1 Receptor Blockers; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; C497443:Hif1a protein, mouse; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007093:Imidazoles; D007375:Interleukin-1; D015850:Interleukin-6; D009687:Nuclear Proteins; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D011993:Recombinant Fusion Proteins; D013777:Tetrazoles; C508961:Tgfb1 protein, mouse; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D018799:Intercellular Adhesion Molecule-1; D000068557:Olmesartan Medoxomil; D040301:Vascular Endothelial Growth Factor Receptor-2; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains