Local Expression of Bovine Decorin by Cell-Mediated Gene Transfer Reduces Neointimal Formation After Balloon Injury in Rats

Fischer, Jens W.; Kinsella, Michael G.; Clowes, Monika M.; Lara, Stephanie; Clowes, Alexander W.; Wight, Thomas N.

doi:10.1161/01.res.86.6.676

Cited by 49 publications

(47 citation statements)

References 49 publications

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“…Cell-mediated gene transfer of decorin at the site of arterial injury resulted in a significant reduction in neointima four weeks after injury (31).…”

Section: Anti-tgf-â Strategiesmentioning

confidence: 97%

Transforming Growth Factor‐β:A Promising Target for Anti‐Stenosis Therapy

Chamberlain

2001

Cardiovascular Drug Reviews

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Transforming growth factor-â (TGF-â) is the general name for a family of cytokines which have widespread effects on many aspects of growth and development. The TGF-â isoforms are produced by most cell types and exert a wide range of effects in a context-dependent autocrine, paracrine or endocrine fashion via interactions with distinct receptors on the cell surface. TGF-â is involved in the wound healing process and, thus plays a significant role in the formation of a restenotic lesion after percutaneous transluminal coronary angioplasty (PTCA) or stenting. Perhaps because of its wide-ranging effects, TGF-â is usually released from cells in a latent form, and its activation and signaling are complex. Manipulation of the TGF-â1, TGF-â2, and TGF-â3 isoforms by inhibiting their expression, activation, or signaling reduces scarring and fibrosis in animal models. However, to date, few have reached clinical trial. This review summarizes current knowledge on the activation and signaling of TGF-â, and focuses on the anti-TGF-â strategies which may lead to clinical applications in the prevention of restenosis following PTCA or stenting.

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“…Cell-mediated gene transfer of decorin at the site of arterial injury resulted in a significant reduction in neointima four weeks after injury (31).…”

Section: Anti-tgf-â Strategiesmentioning

confidence: 97%

Transforming Growth Factor‐β:A Promising Target for Anti‐Stenosis Therapy

Chamberlain

2001

Cardiovascular Drug Reviews

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“…Several extracellular matrix proteins, including adiponectin, decorin, and vasorin, can antagonize the response of vascular cells to growth factors and cytokines by directly binding to them (34)(35)(36)(37). Thus, it is reasonable to speculate that fbln-5 may bind extracellular ligand (s) and prevent them from binding to their receptors.…”

Section: Suppression Of Smc Proliferation and Migration By Fbln-5mentioning

confidence: 99%

Altered vascular remodeling in fibulin-5-deficient mice reveals a role of fibulin-5 in smooth muscle cell proliferation and migration

Spencer

Hacker

Davis

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

107

101

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Fibulin (fbln)-5 is an elastin-binding protein required for assembly and organization of elastic fibers. To examine the potential role of fbln-5 in vascular remodeling and neointima formation, we induced vascular injury by carotid artery ligation in fbln-5 ؊/؊ mice. Mutant mice displayed an exaggerated vascular remodeling response that was accompanied by severe neointima formation with thickened adventitia. These abnormalities were not observed in elastin ؉/؊ mice that exhibited a comparable reduction of vessel extensibility to fbln-5 ؊/؊ mice. Thus, the severe remodeling response could not be attributed to altered extensibility of the vessel wall alone. Vascular smooth muscle cells cultured from fbln-5 ؊/؊ mice displayed enhanced proliferative and migratory responses to mitogenic stimulation relative to wild-type cells, and these responses were inhibited by overexpression of fbln-5. These findings demonstrate the importance of the elastic laminae in vascular injury, and reveal an unexpected role of fbln-5 as an inhibitor of vascular smooth muscle cell proliferation and migration.elastic fibers ͉ extracellular matrix ͉ neointima ͉ elastin V ascular obstructive abnormalities, such as atherosclerosis and restenosis after percutaneous coronary intervention, are triggered by damage to the vessel wall, initiating a series of biological responses, including up-regulation of adhesion molecules, recruitment of inflammatory cells, secretion of cytokines, and activation of smooth muscle cells (SMCs). Activated SMCs secrete growth factors, extracellular matrix proteins, and matrix proteases, thereby altering the microenvironment of the injured vessel wall. Much attention has focused on the signaling pathways responsible for the proliferation and migration of SMCs associated with vascular obstruction, but relatively little is known of the potential contributions of extracellular matrix proteins to these processes (reviewed in ref. 1).Structural changes of the vessel wall induced by mechanical force or enzymatic digestion also influence the development of vascular obstructive disease (2, 3). The elastic lamina plays a critical role in maintaining the integrity of the vessel wall. Rupture of the external elastic lamina (EEL) is a more potent stimulus for neointima formation than injury involving the internal elastic lamina (IEL) alone after coronary artery stent-induced injury (4). In addition, exposure of the adventitia to the blood lumen by disruption of the EEL during percutaneous angioplasty increases the activation of adventitial myofibroblasts, leading to adventitial fibrosis that eventually constricts the vessel wall (5).The perception of the elastic lamina (or elastic fibers) as the sole structural component of the vessel wall was recently challenged by the view that elastic fibers actively modulate intercellular signaling. Elastin (eln), a major component of the elastic fibers in the arterial wall, inhibits proliferation of SMCs (6). Eln is secreted as a tropoelastin monomer and subsequently undergoes cross-linking t...

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“…Neointimal decorin accumulation is a late event after arterial injury and is not upregulated up to 8 weeks after balloon denudation. 33 From 2 to 6 months, stented porcine coronary arteries show a reduction in neointimal hyaluronan associated with reduced neointimal type III and increased type I collagen. 34 …”

Section: Experimental Animal Studies Of Ecm Developmentmentioning

confidence: 99%

“…For example, rat balloon-injured carotid arteries that overexpress bovine decorin via gene transfer demonstrate reduced neointimal size and reduced versican staining with increased type I collagen. 33 …”

Section: Farb Et Al Matrix Of In-stent Neointima 945mentioning

confidence: 99%

Extracellular Matrix Changes in Stented Human Coronary Arteries

et al. 2004

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Background-Restenosis after stenting occurs secondary to the accumulation of smooth muscle cells (SMCs) and extracellular matrix (ECM), with the ECM accounting for Ͼ50% of the neointimal volume. The composition of the in-stent ECM has not been well characterized in humans. Methods and Results-Postmortem human coronary arteries (nϭ45) containing stents underwent histological assessment of neointimal proteoglycans, hyaluronan, collagen (types I and III), SMCs, and CD44 (a cell surface receptor for hyaluronan). The mean duration of stent implantation was 18.7 months; stents in place Ն3 to Ͻ9 months (nϭ17) were assigned to group 1, stents Ն9 to Ͻ18 months old (nϭ19) to group 2, and stents Ն18 months old (nϭ9) to group 3. In groups 1 and 2, neointimal versican and hyaluronan staining was strongly positive, colocalized with ␣-actin-positive SMCs, and was greater in intensity compared with group 3. Conversely, decorin staining was greatest in group 3. The neointima of both group 1 and 2 stents was rich in type III collagen, with reduced staining in group 3. Type I collagen staining was weakest in group 1 stents, with progressively stronger staining in groups 2 and 3. SMC density and stent stenosis were significantly reduced in group 3 stents compared with groups 1 and 2. CD44 staining colocalized with macrophages and was associated with increased neointimal thickness. Conclusions-The ECM within human coronary stents resembles a wound that is not fully healed until 18 months after deployment, followed by neointimal retraction. ECM contraction may be a target for therapies aimed at stent restenosis prevention.

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Local Expression of Bovine Decorin by Cell-Mediated Gene Transfer Reduces Neointimal Formation After Balloon Injury in Rats

Cited by 49 publications

References 49 publications

Transforming Growth Factor‐β:A Promising Target for Anti‐Stenosis Therapy

Transforming Growth Factor‐β:A Promising Target for Anti‐Stenosis Therapy

Altered vascular remodeling in fibulin-5-deficient mice reveals a role of fibulin-5 in smooth muscle cell proliferation and migration

Extracellular Matrix Changes in Stented Human Coronary Arteries

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