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Circulation Research. 2001;89:1111-1121
doi: 10.1161/hh2401.100844
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(Circulation Research. 2001;89:1111.)
© 2001 American Heart Association, Inc.


Reviews

Contribution of Adventitial Fibroblasts to Neointima Formation and Vascular Remodeling

From Innocent Bystander to Active Participant

Saverio Sartore, Angela Chiavegato, Elisabetta Faggin, Rafaella Franch, Massimo Puato, Simonetta Ausoni, Paolo Pauletto

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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J. Perree, T. G. van Leeuwen, R. Kerindongo, J. A. E. Spaan, and E. VanBavel
Function and Structure of Pressurized and Perfused Porcine Carotid Arteries: Effects of in Vitro Balloon Angioplasty
Am. J. Pathol., November 1, 2003; 163(5): 1743 - 1750.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
R. J. Kelm Jr., S.-X. Wang, J. A. Polikandriotis, and A. R. Strauch
Structure/Function Analysis of Mouse Pur{beta}, a Single-stranded DNA-binding Repressor of Vascular Smooth Muscle {alpha}-Actin Gene Transcription
J. Biol. Chem., October 3, 2003; 278(40): 38749 - 38757.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
R. C.M Siow, C. M Mallawaarachchi, and P. L Weissberg
Migration of adventitial myofibroblasts following vascular balloon injury: insights from in vivo gene transfer to rat carotid arteries
Cardiovasc Res, July 1, 2003; 59(1): 212 - 221.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
M. Wang, G. Takagi, K. Asai, R. G. Resuello, F. F. Natividad, D. E. Vatner, S. F. Vatner, and E. G. Lakatta
Aging Increases Aortic MMP-2 Activity and Angiotensin II in Nonhuman Primates
Hypertension, June 1, 2003; 41(6): 1308 - 1316.
[Abstract] [Full Text] [PDF]


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Circ. Res.Home page
A. Diez-Juan and V. Andres
Coordinate Control of Proliferation and Migration by the p27Kip1/Cyclin-Dependent Kinase/Retinoblastoma Pathway in Vascular Smooth Muscle Cells and Fibroblasts
Circ. Res., March 7, 2003; 92(4): 402 - 410.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
W.-J. Cai, S. Koltai, E. Kocsis, D. Scholz, S. Kostin, X. Luo, W. Schaper, and J. Schaper
Remodeling of the adventitia during coronary arteriogenesis
Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H31 - H40.
[Abstract] [Full Text] [PDF]


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ChestHome page
K. R. Stenmark, E. Gerasimovskaya, R. A. Nemenoff, and M. Das
Hypoxic Activation of Adventitial Fibroblasts: Role in Vascular Remodeling
Chest, December 1, 2002; 122 (2009): 326S - 334S.
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CirculationHome page
G. Li, S. Oparil, S. S. Kelpke, Y.-F. Chen, and J. A. Thompson
Fibroblast Growth Factor Receptor-1 Signaling Induces Osteopontin Expression and Vascular Smooth Muscle Cell-Dependent Adventitial Fibroblast Migration In Vitro
Circulation, August 13, 2002; 106(7): 854 - 859.
[Abstract] [Full Text] [PDF]