Circulation Research. 2001;89:1111-1121
doi: 10.1161/hh2401.100844
doi: 10.1161/hh2401.100844
© 2001 American Heart Association, Inc.
Reviews |
Contribution of Adventitial Fibroblasts to Neointima Formation and Vascular Remodeling
From Innocent Bystander to Active Participant
From the Department of Biomedical Sciences (S.S., A.C., R.F., S.A.) and Clinical and Experimental Medicine (E.F., M.P., P.P.) and National Research Council Unit for Muscle Biology and Physiopathology (S.S., S.A.), University of Padua, Italy.
Correspondence to Simonetta Ausoni, PhD, Department of Biomedical Sciences, University of Padua, Viale G. Colombo, 3 I-35121 Padua, Italy. E-mail ausoni{at}civ.bio.unipd.it
Abstract
The adventitial layer surrounding the blood vessels has long been exclusively considered a supporting tissue the main function of which is to provide adequate nourishment to the muscle layers of tunica media. Although functionally interconnected, the adventitial and medial layers are structurally interfaced at the external elastic lamina level, clearly distinguishable at the maturational phase of vascular morphogenesis. Over the last few years the "passive" role that the adventitia seemed to play in experimental and spontaneous vascular pathologies involving proliferation, migration, differentiation, and apoptosis of vascular smooth muscle cells (VSMCs) has been questioned. It has been demonstrated that fibroblasts from the adventitia display an important partnership with the resident medial VSMCs in terms of phenotypic conversion, proliferation, apoptotic, and migratory properties the result of which is neointima formation and vascular remodeling. This article is an attempt at reviewing the major themes and more recent findings dealing with the phenotypic conversion process that leads adventitial "passive" (static) fibroblasts to become "activated" (mobile) myofibroblasts. This event shows some facets in common with vascular morphogenesis, ie, the process of recruitment, incorporation, and phenotypic conversion of cells surrounding the primitive endothelial tube in the definitive vessel wall. We hypothesize that during the response to vascular injuries in the adult, "activation" of adventitial fibroblasts is, at least in part, reminiscent of a developmental program that also invests, although with distinct spatiotemporal features, medial VSMCs.
Key Words: adventitia • vascular smooth muscle cells • myofibroblasts • neointima formation and vascular remodeling
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|
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|
|
|
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|
|
|
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|
|
|
|
|
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|
|
|
|
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|
|
|
|
|
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|
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|
|
|
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|
|
|
|
|
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|
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|
|
|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
T. Yoshida and G. K. Owens Molecular Determinants of Vascular Smooth Muscle Cell Diversity Circ. Res., February 18, 2005; 96(3): 280 - 291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Camelliti, T. K. Borg, and P. Kohl Structural and functional characterisation of cardiac fibroblasts Cardiovasc Res, January 1, 2005; 65(1): 40 - 51. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. G. Kallapur, C. J. Bachurski, T. D. L. Cras, S. N. Joshi, M. Ikegami, and A. H. Jobe Vascular changes after intra-amniotic endotoxin in preterm lamb lungs Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1178 - L1185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
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|
|
|
|
 |
|
 H Nakayama, H Enzan, E Miyazaki, N Kuroda, M Toi, M Hiroi, and W Yasui Presence of vascular adventitial fibroblastic cells in diffuse-type gastric carcinomas J. Clin. Pathol., September 1, 2004; 57(9): 970 - 972. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Puato, E. Faggin, E. Favaretto, B. Bertipaglia, M. Rattazzi, D. Rizzoni, G. P. Gamba, S. Sartore, E. A. Rosei, A. C. Pessina, et al. Prevalence of Fetal-Type Smooth Muscle Cells in the Media of Microvessels From Hypertensive Patients Hypertension, August 1, 2004; 44(2): 191 - 194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. K. Owens, M. S. Kumar, and B. R. Wamhoff Molecular Regulation of Vascular Smooth Muscle Cell Differentiation in Development and Disease Physiol Rev, July 1, 2004; 84(3): 767 - 801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Cooley Murine Model of Neointimal Formation and Stenosis in Vein Grafts Arterioscler. Thromb. Vasc. Biol., July 1, 2004; 24(7): 1180 - 1185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
 R. Vattikuti and D. A. Towler Osteogenic regulation of vascular calcification: an early perspective Am J Physiol Endocrinol Metab, May 1, 2004; 286(5): E686 - E696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Davie, J. T. Crossno Jr., M. G. Frid, S. E. Hofmeister, J. T. Reeves, D. M. Hyde, T. C. Carpenter, J. A. Brunetti, I. K. McNiece, and K. R. Stenmark Hypoxia-induced pulmonary artery adventitial remodeling and neovascularization: contribution of progenitor cells Am J Physiol Lung Cell Mol Physiol, April 1, 2004; 286(4): L668 - L678. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. T. Choi, M. F. Khan, J. E. Leidenfrost, E. T. Collins, K. P. Boc, B. R. Villa, D. V. Novack, W. C. Parks, and D. R. Abendschein {beta}3-Integrin Mediates Smooth Muscle Cell Accumulation in Neointima After Carotid Ligation in Mice Circulation, March 30, 2004; 109(12): 1564 - 1569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H Nakayama, H Enzan, E Miyazaki, N Kuroda, M Toi, M Hiroi, and W Yasui Lack of vascular adventitial fibroblastic cells in tumour stroma of intestinal-type and solid-type gastric carcinomas J. Clin. Pathol., February 1, 2004; 57(2): 183 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Short, R. A. Nemenoff, W. M. Zawada, K. R. Stenmark, and M. Das Hypoxia induces differentiation of pulmonary artery adventitial fibroblasts into myofibroblasts Am J Physiol Cell Physiol, February 1, 2004; 286(2): C416 - C425. [Abstract] [Full Text]
|
|
|
|
 |
|
 I. Dobreva, G. Waeber, V. Mooser, R. W. James, and C. Widmann LDLs induce fibroblast spreading independently of the LDL receptor via activation of the p38 MAPK pathway J. Lipid Res., December 1, 2003; 44(12): 2382 - 2390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
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|
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