Remodeling of Carotid Artery Is Associated With Increased Expression of Matrix Metalloproteinases in Mouse Blood Flow Cessation Model

Godin, Denis; Ivan, Eugen; Johnson, Craig B.; Magid, Richard; Galis, Zorina S.

doi:10.1161/01.cir.102.23.2861

Cited by 182 publications

(171 citation statements)

References 42 publications

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“…14,19 Because of differences in the hemodynamic environment in which lesion growth occurs, this model cannot perfectly reproduce the process of spontaneous lesion development at vulnerable locations in the vasculature of the apoE KO mouse. Nevertheless, histological assessment confirms that, by 14 days after ligation, lesions initiated by this procedure in the apoE KO mouse display many of the features typical of advanced plaques in this model, 20 including involvement of multiple cell types (SMCs, macrophages, T lymphocytes), formation of cholesterol crystals, and differentiation of fibrous cap and lipid-rich core regions.…”

Section: Discussionmentioning

confidence: 99%

“…Approximately 8 weeks after BMT, formation of arterial lesions was induced in recipient mice by ligation of the left common carotid artery according to our previously published method 14 and the mice were placed on an atherogenic diet. Groups of four to eight mice were sacrificed by means of CO 2 asphyxiation after 3, 7, or 14 days on diet.…”

Section: Experimental Model Of Atherosclerosismentioning

confidence: 99%

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Atherosclerotic Lesions Grow Through Recruitment and Proliferation of Circulating Monocytes in a Murine Model

Lessner

Prado

Waller

et al. 2002

The American Journal of Pathology

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153

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Macrophage-derived foam cells in developing atherosclerotic lesions may potentially originate either from recruitment of circulating monocytes or from migration of resident tissue macrophages. In this study, we have determined the source of intimal macrophages in the apoE-knockout mouse flow-cessation/hypercholesterolemia model of atherosclerosis using a bone marrow transplantation approach. We also examined the time course and spatial distribution of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression to assess whether endothelial adhesion molecules were involved in recruitment of either circulating monocytes or resident macrophages. We used allelic variants of the mouse common leukocyte antigen (CD45) to distinguish host-derived and donor-derived white blood cells (WBCs) both in blood and in macrophage-rich carotid lesions. We found that the distribution of CD45 isoforms in lesions is similar to that of circulating WBCs, whereas the host-type CD45 isoform is more prevalent in resident adventitial macrophages. These data indicate that macrophage-derived foam cells in the lesion derive mainly from circulating precursors rather than from resident macrophages. The corresponding time course of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression suggests that recruitment of circulating WBCs by endothelial adhesion molecules is likely to be more important during lesion initiation than during the later phase of rapid lesion growth. Both in experimental models of atherosclerosis and in human disease, infiltration of macrophages into the arterial intima constitutes one of the earliest cellular events in the development of atherosclerotic lesions. 1-3 Macrophages in the lesion may be derived either from cells already resident in the arterial wall 4 or from circulating monocytes that have undergone diapedesis. Because the mechanisms of cellular recruitment and/or activation are likely to differ depending on the source of the inflammatory cells, determining the relative contribution to lesion growth of cells from these two sources may have important implications in devising successful strategies to slow the growth of lesions.Although much convincing evidence demonstrates the importance of blood-borne monocytes in early lesion development, 1,5,6 the potential contribution of resident macrophages has been more difficult to assess. Experiments involving injection of labeled tracer monocytes can provide estimates for the rate of recruitment of circulating inflammatory cells but do not directly address the issue of mobilization of macrophages already present in arterial tissue. Moreover, alterations in adhesion molecule expression that can occur during monocyte isolation and labeling may modify the interaction between circulating monocytes and the vascular wall. The recent development of a polymerase chain reaction-based method of quantifying monocyte recruitment has shown promise of improved sensitivity and ease of quantitation compared to more traditional approach...

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Section: Discussionmentioning

confidence: 99%

Section: Experimental Model Of Atherosclerosismentioning

confidence: 99%

Atherosclerotic Lesions Grow Through Recruitment and Proliferation of Circulating Monocytes in a Murine Model

Lessner

Prado

Waller

et al. 2002

The American Journal of Pathology

Self Cite

153

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“…The ligated carotid artery undergoes initial outward remodeling, followed by vessel shrinkage and neointima formation, resulting in narrowing of the lumen (22). To examine whether the loss of fbln-5 affected the vascular response to injury, we first compared the remodeling of the vessel 28 days after the ligation in wild-type and fbln-5 Ϫ/Ϫ left carotid arteries.…”

Section: Increased Vessel Diameter and Neointima Formation In Fbln-5 ؊/؊mentioning

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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“…19 Specifically, increased MMP-2 and MMP-9 expression has been demonstrated in response to altered blood flow 20,21 and hypertension, 22 while altered axial strain caused sustained MMP-2 expression but only transient MMP-9 expression 23,24 in arteries in vivo. Altered shear stress also produces soluble factors such as nitric oxide (NO) 25 that lead to MMP production and release in an NF-kB (p50=p65 subunit)-dependent response.…”

mentioning

confidence: 99%

Hemodynamics and Axial Strain Additively Increase Matrix Remodeling and MMP-9, But Not MMP-2, Expression in Arteries Engineered by Directed Remodeling

Nichol

Khan

Birbach

et al. 2009

Tissue Engineering Part A

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We previously demonstrated the ability to create engineered arteries by carefully controlling the mechanical environment of intact arteries perfused ex vivo, yielding engineered arteries with native appearance and vasoactive response. Increased axial strain was sufficient to increase length up to 20% in 9 days through a growth and remodeling response. The amount of the achievable length increase, however, was highly dependent on the hemodynamic conditions acting through unknown mechanisms. Because matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) activity is increased, and often required, in mechanically induced remodeling in vivo, MMP-2 and MMP-9 expression was investigated to elucidate the hemodynamic mediation of artery length. Carotid arteries from 30 kg pigs were perfused for 9 days ex vivo at either in situ axial strain or with a gradual 50% increase in axial strain, under either arterial or reduced hemodynamics (*10% of arterial hemodynamics). MMP-2 protein expression increased roughly twofold, while MMP-9 expression increased threefold under either reduced hemodynamics or increased axial strain ( p < 0.05). The combination of reduced hemodynamics with increased axial strain demonstrated an additive increase in MMP-9 protein ( p < 0.05) with no further change in MMP-2 expression. To investigate the mechanism by which axial strain and hemodynamics could additively increase MMP-9 expression, the expression of nuclear factor kappa B (NF-kB) subunits p50 and p65 was evaluated. Axial strain stimulated p65 expression and localization, while hemodynamics increased p50 expression, with both molecules being expressed only when both mechanical stimuli were applied. These data suggest that MMP-9 expression can be simultaneously stimulated by separate mechanical stimuli mediated by p50 and p65 expression, and that by using conditions that maximize MMP-9 expression, we can create an optimal remodeling environment to better direct the growth of engineered arteries and other tissues.

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Remodeling of Carotid Artery Is Associated With Increased Expression of Matrix Metalloproteinases in Mouse Blood Flow Cessation Model

Cited by 182 publications

References 42 publications

Atherosclerotic Lesions Grow Through Recruitment and Proliferation of Circulating Monocytes in a Murine Model

Atherosclerotic Lesions Grow Through Recruitment and Proliferation of Circulating Monocytes in a Murine Model

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

Hemodynamics and Axial Strain Additively Increase Matrix Remodeling and MMP-9, But Not MMP-2, Expression in Arteries Engineered by Directed Remodeling

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