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  • Berk, Bradford C.  (5)
  • 2000-2004  (5)
  • 1
    Online Resource
    Online Resource
    Flow-Induced Vascular Remodeling in the Mouse : A Model for Carotid Intima-Media Thickening
    Ovid Technologies (Wolters Kluwer Health) ; 2003
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 23, No. 12 ( 2003-12), p. 2185-2191
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 23, No. 12 ( 2003-12), p. 2185-2191
    Abstract: Objective— Vascular remodeling of the carotid artery with intima-media thickness (IMT) is an important predictive factor for human cardiovascular disease. We characterized a mouse model of vascular remodeling. Methods and Results— The left external and internal carotid branches were ligated so that left carotid blood flow was reduced to flow via the occipital artery. In response to partial ligation of the left carotid artery (LCA), blood flow significantly decreased (−90%) in the LCA and increased (+70%) in the right carotid artery (RCA). Morphometry showed that both RCA and LCA underwent outward remodeling that was maximal at one week. Remodeling was greater in the RCA with predominantly increased lumen and very little increase in media or adventitia. In the LCA there was a dramatic increase in media with adventitia growth and intima formation. Correlation analysis indicated that the outward remodeling was more likely due to primary changes in the vessel wall rather than to changes in the lumen, such as shear stress. Mechanistic studies suggested roles for macrophage infiltration, upregulation of matrix metalloproteinase (MMP)-9, extracellular matrix reorganization, and vascular smooth muscle cell proliferation in LCA remodeling. Conclusions— The mouse model described here may be useful to define genetic determinants of IMT and identify new targets for therapy based on vascular remodeling.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/01.ATV.0000103120.06092.14
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2003
    detail.hit.zdb_id: 1494427-3
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  • 2
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    Role of Angiotensin-Converting Enzyme and Neutral Endopeptidase in Flow-Dependent Remodeling
    S. Karger AG ; 2004
    In:  Journal of Vascular Research Vol. 41, No. 2 ( 2004), p. 148-156
    Details
    In: Journal of Vascular Research, S. Karger AG, Vol. 41, No. 2 ( 2004), p. 148-156
    Abstract: Omapatrilat inhibits neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE). We compared the effects of omapatrilat (40 mg/kg/day, p.o.) to fosinopril (40 mg/kg/day, p.o.) on flow-induced vascular remodeling in New Zealand genetically hypertensive (GH) rats. Both drugs equally reduced blood pressure (BP) initially, but systolic BP and pulse pressure were reduced more by omapatrilat after 1 week. Carotid remodeling was induced by partial ligation of the left common carotid artery (LCA). There was little remodeling in untreated GH rats – measured as outer diameter to body weight (OD/BW vs. before ligation): 97 ± 1% of initial LCA (low flow) and 107 ± 3% of initial right common carotid artery (RCA, high flow). In contrast, OD/BW increased to 118 ± 5% (p 〈 0.05) of initial RCA after omapatrilat versus 108 ± 2% (p = 0.96) after fosinopril. The major change was increased RCA lumen area which was significantly larger in omapatrilat-treated animals (127% vs. control) than fosinopril-treated animals (103% vs. control). The increase in outward remodeling after omapatrilat treatment correlated weakly with vascular cGMP levels and decreased systolic BP. The results suggest that dual inhibition of NEP/ACE may have greater effects than ACE inhibition alone on vessel remodeling in hypertension.
    Type of Medium: Online Resource
    ISSN: 1018-1172 , 1423-0135
    URL: Article
    DOI: 10.1159/000077144
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2004
    detail.hit.zdb_id: 1482726-8
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  • 3
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    Online Resource
    Plasminogen Activator Expression Correlates with Genetic Differences in Vascular Remodeling
    S. Karger AG ; 2004
    In:  Journal of Vascular Research Vol. 41, No. 6 ( 2004), p. 481-490
    Details
    In: Journal of Vascular Research, S. Karger AG, Vol. 41, No. 6 ( 2004), p. 481-490
    Abstract: Intima-media thickening (IMT) of the carotid artery, a form of vascular remodeling, correlates well with coronary artery disease risk in humans. Vascular remodeling in response to blood flow is a complex process that critically involves altered cell matrix interactions. To gain insight into these events, we performed partial carotid ligation (left carotid (LCA) = low flow and right carotid (RCA) = high flow) in 2 inbred mouse strains: C57Bl/6J (C57) and FVB/NJ (FVB). To evaluate the role of the 2 major matrix-degrading systems, plasminogen activators (PAs) and matrix metalloproteinases (MMPs), we compared the expression of u-PA, t-PA, MMP-2 and MMP-9 in ligated carotids of C57 and FVB mice. The extent of remodeling was greater in response to low LCA than high RCA flow. Despite a similar decrease in LCA flow in both strains, maximal IMT volume was greater in FVB (82 ± 7 × 10 〈 sup 〉 –6 〈 /sup 〉 µm 〈 sup 〉 3 〈 /sup 〉 ) than in C57 (38 ± 4 × 10 〈 sup 〉 –6 〈 /sup 〉 µm 〈 sup 〉 3 〈 /sup 〉 ) after ligation. Among PAs and MMPs, increased expression of t-PA and u-PA correlated with increased IMT (p 〈 0.0005 and p 〈 0.001, respectively). MMP-2, MMP-9 and tissue inhibitors of metalloproteinase-2 expression also increased, but did not differ between strains. In summary, flow-induced IMT of the carotid is genetically determined and correlates with t-PA and u-PA expression in 2 inbred mouse strains.
    Type of Medium: Online Resource
    ISSN: 1018-1172 , 1423-0135
    URL: Article
    DOI: 10.1159/000081804
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2004
    detail.hit.zdb_id: 1482726-8
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  • 4
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    Strain-Dependent Vascular Remodeling : The “Glagov Phenomenon” Is Genetically Determined
    Ovid Technologies (Wolters Kluwer Health) ; 2004
    In:  Circulation Vol. 110, No. 2 ( 2004-07-13), p. 220-226
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 110, No. 2 ( 2004-07-13), p. 220-226
    Abstract: Background— Atherosclerosis of the carotid artery, called intima-media thickening (IMT), is a form of vascular remodeling that is an important predictor for cardiovascular events and has a strong genetic component. Methods and Results— Recently, we established a mouse model of vascular remodeling based on partial ligation of the carotid, which is relevant to the “Glagov phenomenon.” We hypothesized that there would be genetically determined differences in outward remodeling and IMT induced by carotid flow alterations. We compared vascular remodeling among 5 inbred strains of mice. Despite similar changes in flow among the strains in the left carotid artery (LCA), we observed dramatic differences in remodeling of the partially ligated LCA relative to control. The smallest IMT volume (26±3 μm 3 ) was found in C3H/HeJ mice, and the largest were in SJL/J (59±10 μm 3 ) and FVB/NJ (81±6 μm 3 ). Shear stress did not differ after ligation among strains. Lumen area decreased only when stenosis was ≥55%. IMT correlated significantly with outward remodeling among inbred strains (except C3H). There were significant strain-dependent differences in remodeling index (measured as vessel area/IMT), which suggest fundamental alterations in sensing or transducing hemodynamic signals among strains. Among hemodynamic factors, low shear stress and high heart rate were predictive for IMT. Specifically, heart rate (bpm: C3H, 592±6; SJL, 649±6; FVB, 683±7) but not systolic blood pressure (mm Hg: C3H, 116±2; SJL, 119±1; FVB, 136±1) was predictive. Conclusions— The present study indicates that performing a genetic cross of these strains and total genome scan should identify genes that mediate vascular remodeling.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.0000134958.88379.2E
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2004
    detail.hit.zdb_id: 1466401-X
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  • 5
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    Hydrogen Peroxide Activates the Gas6-Axl Pathway in Vascular Smooth Muscle Cells
    Elsevier BV ; 2004
    In:  Journal of Biological Chemistry Vol. 279, No. 27 ( 2004-07), p. 28766-28770
    Details
    In: Journal of Biological Chemistry, Elsevier BV, Vol. 279, No. 27 ( 2004-07), p. 28766-28770
    Type of Medium: Online Resource
    ISSN: 0021-9258
    URL: Article
    DOI: 10.1074/jbc.M401977200
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2004
    detail.hit.zdb_id: 2141744-1
    detail.hit.zdb_id: 1474604-9
    SSG: 12
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