Intimal lesion formation in rat carotid arteries after endothelial denudation in absence of medial injury.

Fingerle, Jürgen; Au, Y P; Clowes, A. W.; Reidy, Michael A.

doi:10.1161/01.atv.10.6.1082

Cited by 171 publications

(102 citation statements)

References 17 publications

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“…This experiment was based on our experience with vascular injury models in which the magnitude of medial SMC proliferation correlates with the amount of damage (loss of DNA) inflicted on the vessel wall. 20,21 As we have previously shown, fibroblast growth factor-2 released from lethally and sublethally damaged cells is a key player in the onset of medial SMC proliferation. Nearly 37% of medial SMC were lost from the media within 2 days after ligation (ie, before SMC division occurs) in FVB/NJ carotid arteries, whereas no loss was detectable in the C3H/HeJ mice.…”

Section: Discussionmentioning

confidence: 96%

“…20,21 We have also shown that the trauma-induced proliferation of SMC in the rat balloon injury model is mediated by the release of fibroblast growth factor-2 from damaged cells. 22,23 Furthermore, we have previously noted a loss of medial SMC in the carotid artery of FVB/NJ mice occurring within the first 2 days after ligation of the vessel.…”

Section: Loss Of Smc In Response Carotid Artery Ligationmentioning

confidence: 87%

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Strain-Dependent Vascular Remodeling Phenotypes in Inbred Mice

Harmon¹,

Couper²,

Lindner³

2000

The American Journal of Pathology

120

104

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Vascular remodeling is a response of blood vessels to both physiological and pathological stimuli, leading to either vessel enlargement (positive remodeling) or reduction in vessel diameter (negative remodeling). Examples of remodeling have been observed in fetal development 1 and after graft placement 2-5 or angioplasty. 6 -8 In humans, vascular remodeling but not intimal lesion formation was shown to account for the majority of the restenosis in response to angioplasty procedures. 9,10 We have recently established and characterized a mouse model of arterial remodeling. 11 In this model, flow in the common carotid artery is interrupted by ligation of the vessel near the carotid bifurcation. Using FVB/NJ mice, this resulted in a dramatic reduction in vessel diameter and formation of an intimal lesion. Neointima formation and the influx of inflammatory cells in this model are reduced in P-selectin-deficient mice, while the reduction in vessel diameter is not affected by the lack of P-selectin. 12 Additional specific factors that mediate the remodeling response are beginning to emerge. Several studies have implicated nitric oxide (NO) as an inhibitor of remodeling events. [13][14][15][16][17] Our own studies demonstrated that alterations in blood flow also lead to changes in gene expression of platelet-derived growth factor Achain and B-chain, factors known to modulate proliferation and migration of smooth muscle cells (SMC). 18 Preliminary experiments in our laboratory indicated that there is wide qualitative and quantitative variation in the vascular remodeling response of different mouse strains. To provide the basis for a genetic analysis, we subjected 11 different strains of inbred mice to carotid artery ligation for analysis of the remodeling response. Large differences were found between strains with regards to negative as well as positive remodeling and intimal lesion formation. The magnitude of neointima formation correlated with increased loss of SMC occurring immediately after ligation of the carotid artery as well as enhanced growth properties of SMC in vitro.

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Section: Discussionmentioning

confidence: 96%

Section: Loss Of Smc In Response Carotid Artery Ligationmentioning

confidence: 87%

Strain-Dependent Vascular Remodeling Phenotypes in Inbred Mice

Harmon¹,

Couper²,

Lindner³

2000

The American Journal of Pathology

120

104

View full text Add to dashboard Cite

show abstract

“…(23). Various models of vascular injury have been introduced, including denudation of the endothelium by mechanical injury (wire, balloon catheters) (24,25). Luminal mechanical injury leads to endothelial denudation and platelet activation, which contribute to inflammatory cell recruitment.…”

Section: Discussionmentioning

confidence: 99%

The A2b adenosine receptor protects against vascular injury

Yang

Koupenova

McCrann

et al. 2008

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

114

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The A2b adenosine receptor (A2bAR) is highly abundant in bone marrow macrophages and vascular smooth muscle cells (VSMC). To examine the functional significance of this receptor expression, we applied a femoral artery injury model to A2bAR knockout (KO) mice and showed that the A2bAR prevents vascular lesion formation in an injury model that resembles human restenosis after angioplasty. While considering related mechanisms, we noted higher levels of TNF-␣, an up-regulator of CXCR4, and of VSMC proliferation in the injured KO mice. In accordance, CXCR4, which is known to attract progenitor cells during tissue regeneration, is up-regulated in lesions of the KO mice. In addition, aortic smooth muscle cells derived from A2bAR KO mice display greater proliferation in comparison with controls. Bone marrow transplantation experiments indicated that the majority of the signal for lesion formation in the null mice originates from bone marrow cells. Thus, this study highlights the significance of the A2bAR in regulating CXCR4 expression in vivo and in protecting against vascular lesion formation.inflammation ͉ CXCR4

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“…Rat carotid arteries were injured using either the gentle injury technique previously described (32) or balloon catheter denudation. The catheter was introduced into the left common carotid through the left external branch and passed up and down the common carotid three times to ensure complete denudation.…”

Section: Methodsmentioning

confidence: 99%

“…This procedure completely removes the endothelial cells lining the carotid artery and yet causes only a small increase (1.5%) in medial smooth muscle cell proliferation (32). Denudation is necessary because endothelialized arteries do not respond to systemic infusion of FGF2 (3).…”

Section: Response Of Arterial Smooth Muscle Cell To Exogenousmentioning

confidence: 99%

Proliferation of Intimal Smooth Muscle Cells

Olson

Kozlowski

Reidy

2000

Journal of Biological Chemistry

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Excessive growth of vascular smooth muscle cells is an important component in the development of atherosclerotic lesion and in restenosis. In order to study which factors control the growth of these cells, we and many others have used a model of smooth muscle cell proliferation induced by mechanical injury of the rat carotid artery (1, 2). In this model, an inflated Fogarty balloon catheter is passed into the lumen of the common carotid artery, denuding the artery of its endothelial cell lining and damaging the underlying medial smooth muscle cells. This injury results in a predictable response; within 2 days the medial smooth muscle cells begin proliferating, and after 4 days medial smooth muscle cells migrate into the intima, where they continue to proliferate for up to 2 weeks. This leads to the formation of a thickened neointima comprised primarily of smooth muscle cells and extracellular matrix and results in luminal narrowing. In this model, basic fibroblast factor (FGF2) 1 has been shown to be a critical mitogen for the proliferation of medial smooth muscle cells. The addition of FGF2 significantly increases medial smooth muscle cell proliferation when administered after injury of the rat carotid artery (3), and medial smooth muscle cell proliferation can be significantly inhibited by neutralizing antibodies to FGF2 (4). Unlike medial smooth muscle cells, FGF2 does not seem to be involved in regulating the proliferation of the smooth muscle cells that have migrated into the intima; neutralizing antibodies to FGF2 do not inhibit intimal smooth muscle cell proliferation (5) after balloon catheter injury, and the addition of FGF2 to arteries with existing intimal lesions causes only a small increase in proliferation (3). These data suggest that, in contrast to medial smooth muscle cells, FGF2 is not necessary for intimal smooth muscle cell proliferation, nor is it a potent mitogen for those cells. The purpose of this study was to determine whether differences in the activation of cytoplasmic signaling pathways and/or cell cycle regulation could be responsible for this apparent attenuation of FGF2-stimulated proliferation in intimal smooth muscle cells. FGF2 signal transduction involves the activation of many different cytoplasmic signaling molecules, including the extracellular signal-regulated kinases 1 and 2 (ERKs 1 and 2) (6 -9). Activation of the ERKs is required for FGF2-stimulated proliferation in several different cell types, and recently we have shown that the ERK signaling pathway is activated following balloon catheter denudation of the rat carotid artery and that ERK activity is required for smooth muscle cell proliferation following this injury (10). FGF2 stimulation also activates the PI 3-kinase pathway (11). Activation of this pathway is required for FGF2-stimulated proliferation in a variety of cell types including smooth muscle cells (12), and recent data suggest that this pathway is also activated following balloon catheter injury (10).Although FGF2 stimulation requires activation of cytopl...

show abstract

Intimal lesion formation in rat carotid arteries after endothelial denudation in absence of medial injury.

Cited by 171 publications

References 17 publications

Strain-Dependent Vascular Remodeling Phenotypes in Inbred Mice

Strain-Dependent Vascular Remodeling Phenotypes in Inbred Mice

The A2b adenosine receptor protects against vascular injury

Proliferation of Intimal Smooth Muscle Cells

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