Khurana, R;
Zhuang, Z;
Bhardwaj, S;
Murakami, M;
De Muinck, E;
Yla-Herttuala, S;
Ferrara, N;
... Simons, M; + view all
(2004)
Angiogenesis-dependent and independent phases of intimal hyperplasia.
Circulation
, 110
(16)
pp. 2436-2443.
10.1161/01.CIR.0000145138.25577.F1.
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Abstract
BACKGROUND: Neointimal vascular smooth muscle cell (VSMC) proliferation is a primary cause of occlusive vascular disease, including atherosclerosis, restenosis after percutaneous interventions, and bypass graft stenosis. Angiogenesis is implicated in the progression of early atheromatous lesions in animal models, but its role in neointimal VSMC proliferation is undefined. Because percutaneous coronary interventions result in induction of periadventitial angiogenesis, we analyzed the role of this process in neointima formation. METHODS AND RESULTS: Local injury to the arterial wall in 2 different animal models induced periadventitial angiogenesis and neointima formation. Application of angiogenesis stimulators vascular endothelial growth factor (VEGF-A165) or a proline/arginine-rich peptide (PR39) to the adventitia of the injured artery induced a marked increase in neointimal thickening beyond that seen with injury alone in both in vivo models. Inhibition of either VEGF (with soluble VEGF receptor 1 [sFlt1]) or fibroblast growth factor (FGF) (with a dominant=negative form of FGF receptor 1 [FGF-R1DN]), respectively, signaling reduced adventitial thickening induced by VEGF and PR39 to the level seen with mechanical arterial injury alone. However, neither inhibitor was effective in preventing neointimal thickening after mechanical injury when administered in the absence of angiogenic growth factor. CONCLUSIONS: Our findings indicate that adventitial angiogenesis stimulates intimal thickening but does not initiate it.
| Type: | Article |
|---|---|
| Title: | Angiogenesis-dependent and independent phases of intimal hyperplasia. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1161/01.CIR.0000145138.25577.F1 |
| Keywords: | Angiogenesis Inducing Agents, Animals, Antimicrobial Cationic Peptides, Carotid Artery Injuries, Catheterization, Fibroblast Growth Factor 1, Hyperplasia, Male, Models, Animal, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Neovascularization, Physiologic, Proteins, Rabbits, Rats, Rats, Sprague-Dawley, Receptor Protein-Tyrosine Kinases, Receptor, Fibroblast Growth Factor, Type 1, Receptors, Fibroblast Growth Factor, Recombinant Fusion Proteins, Solubility, Tunica Intima, Vasa Vasorum, Vascular Endothelial Growth Factor A |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/8282 |
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