Kinetics of Bromodeoxyuridine Uptake by Smooth Muscle Cells after Arterial Injury

London, Susan; Mayberg, Marc R.

doi:10.1159/000159050

Cited by 25 publications

(13 citation statements)

References 38 publications

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“…Compared with the very low BrdU labeling index in uninjured vessels (0.03% BrdU-positive cells 22 ), mean BrdU labeling index 5 days after balloon injury was 43Ϯ3% of vascular cells. A significant decrease in the number of BrdU-positive neointimal cells was observed in AdCMVceNOS-infected compared with AdRR5-infected arteries or untransduced, control injured arteries (29Ϯ6% versus 45Ϯ4% and 43Ϯ3% BrdU-labeled cells, respectively, PϽ.05, Fig 6).…”

Section: Pϭns)mentioning

confidence: 73%

Human Endothelial Nitric Oxide Synthase Gene Transfer Inhibits Vascular Smooth Muscle Cell Proliferation and Neointima Formation After Balloon Injury in Rats

et al. 1998

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Background-Loss of endothelial NO production after arterial injury may contribute to restenosis, characterized by neointima formation and elastic recoil. Adenovirus-mediated transfer of the gene encoding NO synthase (NOS) in balloon-injured arteries may restore NO production and inhibit neointima formation. Methods and Results-After balloon injury, rat carotid arteries were transduced with 3ϫ10 10 pfu/mL recombinant adenovirus carrying the human endothelial constitutive NOS cDNA (AdCMVceNOS, nϭ8) or no cDNA (AdRR5, nϭ8). ceNOS expression was confirmed by immunoblot analysis of vascular extracts and was localized by immunostaining in 30% of medial smooth muscle cells (SMCs) and in the adventitia of AdCMVceNOS-transduced arteries. Vascular cGMP levels were reduced from 3.9 pmol/g wet wt in uninjured arteries to 0.7 pmol cGMP/g after AdRR5 but were restored after ceNOS gene transfer (3.8 pmol cGMP/g wet wt, PϽ.05 versus AdRR5). Intima-to-media ratio 2 weeks after injury was significantly reduced (0.19Ϯ0.02 in AdCMVceNOS-infected versus 0.69Ϯ0.07 in AdRR5-infected arteries, PϽ.05). In vitro, BrdU incorporation of AdCMVceNOS-infected SMCs was reduced by 28% compared with AdRR5-infected SMCs. Transduced cells from injured carotid arteries subjected to FACS sorting showed a significantly lower BrdU labeling index in ceNOS-infected rats (29Ϯ6% versus 43Ϯ5% and 45Ϯ4% in control, injured, and AdRR5-infected rats, respectively, PϽ.05). Conclusions-AdCMVceNOS gene transfer to balloon-injured rat carotid arteries restores vascular NO productionand reduces neointima formation, at least in part because of an antiproliferative effect on medial SMCs. Adenovirusmediated ceNOS gene transfer might reduce arterial restenosis after balloon angioplasty. (Circulation. 1998;97:1274-1281.)

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Section: Pϭns)mentioning

confidence: 73%

Human Endothelial Nitric Oxide Synthase Gene Transfer Inhibits Vascular Smooth Muscle Cell Proliferation and Neointima Formation After Balloon Injury in Rats

et al. 1998

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“…Previous studies evaluating the kinetics of cell proliferation after vascular injury with the use of either [ 3 H]thymidine 25 or BrdU 26 found that the proliferation of carotid medial cells peaked at day 2 or 3, whereas neointimal cells peaked at day 4 or 5. Using proliferating cell nuclear antigen, BrdU, and [ 3 H]thymidine autoradiography, Zeymer et al 27 have shown that intimal proliferation was highest 7 days after denudation of rat aortas, when 40% of cells were BrdUϩ.…”

Section: Discussionmentioning

confidence: 99%

Differential Cell Cycle Progression Patterns of Infiltrating Leukocytes and Resident Cells After Balloon Injury of the Rat Carotid Artery

Hay

Micko²,

Prescott³

et al. 2001

ATVB

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Abstract-The heterogeneous nature of the cell populations involved in vascular repair remains a major hurdle for the assessment of the cellular events that take place in injured arteries. The present experiments were designed to estimate the proportions and cell cycle progression of infiltrating leukocytes versus resident vascular cells after balloon injury of the rat common carotid artery. After tissue disaggregation, cell suspension samples from each artery were analyzed by flow cytometry. Cells were stained with anti-CD45 or anti-␣-smooth muscle actin antibodies to identify leukocytes and smooth muscle cells, respectively. A day after injury, a 12-fold increase in CD45ϩ leukocytes was found. Double labeling with CD45 and CD-3, ED-1, or granulocyte markers revealed that most infiltrating cells were monocytes and granulocytes. Approximately 14% of infiltrating leukocytes were found to enter apoptosis at day 1, and 17% entered S phase at day 3. In contrast, the highest proliferation rate of resident ␣-smooth muscle actin-positive cells was observed at day 7 (19% Key Words: restenosis Ⅲ vascular remodeling Ⅲ inflammation Ⅲ flow cytometry Ⅲ apoptosis Q uiescent vascular smooth muscle cells (SMCs) respond to acute vascular injury with an array of phenotypic changes, including proliferation, migration, programmed cell death, and modulation to a less differentiated state. 1-3 Deendothelialization of the carotid artery is followed by proliferation of medial SMCs, with subsequent migration of these cells to the intima, where they proliferate and secrete extracellular matrix. 4 Inflammation is associated with the development of atherosclerotic lesions and is thought to play a critical role in vascular SMC proliferation, migration, and matrix production in response to injury. 5 Interleukin (IL)-1␤ and tumor necrosis factor-␣ may induce the expression of monocyte chemoattractant protein (MCP)-1, IL-8, intercellular adhesion molecule-1, and vascular adhesion molecule (VCAM)-1 to assist the recruitment of leukocytes into a mechanically injured tissue or an atherosclerotic lesion. 6 -9 MCP-1 and MCP-3 have been shown to be upregulated in the neointima, 10,11 and inhibition of intimal proliferation by antibodies (Abs) against MCP-1 supports the role of these molecules in vascular lesion formation. 12 To further evaluate the contribution of proliferating leukocytes to the vascular repair process, we examined the cell cycle status of infiltrating leukocytes and vascular SMCs in vivo by using a well-characterized model of balloon injury. By use of a double-labeling technique, the proliferative and DNA content profiles of vascular SMCs and infiltrating leukocytes were analyzed by flow cytometry. Methods Carotid InjuryBalloon injury of the common carotid artery was performed as described by Clowes et al. 13 To identify proliferating cells, bromodeoxyuridine (BrdU, 50 mg/kg IP, Sigma Chemical Co) was administered 18 hours before tissue harvesting. For the time-course flow cytometric analysis, rats (nϭ4 per time point) were euthaniz...

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“…Previous studies have shown that in response to vascular injury, proliferating SMC may undergo changes in phenotype as judged by reduced or even absent expression of α smooth muscle actin (18)(19)(20). Ten days after the carotid wire injury, α smooth muscle actin expression in arteries of nontransgenic mice was focal and minimal to absent in the thickest part of the vessel wall.…”

Section: Induction Of Elastase Activity After Carotid Arterial Injurymentioning

confidence: 94%

“…Loss of α-actin has been described in balloon injury of carotid arteries (18,20,29), coronary angioplasty (19), and post-transplant arteriosclerosis (30). This loss of α-actin has been attributed to altered phenotype (29) and to proliferation of SMCs (18,20).…”

Section: Figurementioning

confidence: 99%

Suppressed smooth muscle proliferation and inflammatory cell invasion after arterial injury in elafin-overexpressing mice

Zaidi¹,

You²,

Ciura³

et al. 2000

J. Clin. Invest.

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Kinetics of Bromodeoxyuridine Uptake by Smooth Muscle Cells after Arterial Injury

Cited by 25 publications

References 38 publications

Human Endothelial Nitric Oxide Synthase Gene Transfer Inhibits Vascular Smooth Muscle Cell Proliferation and Neointima Formation After Balloon Injury in Rats

Human Endothelial Nitric Oxide Synthase Gene Transfer Inhibits Vascular Smooth Muscle Cell Proliferation and Neointima Formation After Balloon Injury in Rats

Differential Cell Cycle Progression Patterns of Infiltrating Leukocytes and Resident Cells After Balloon Injury of the Rat Carotid Artery

Suppressed smooth muscle proliferation and inflammatory cell invasion after arterial injury in elafin-overexpressing mice

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