Transluminale Angioplastie von experimentell erzeugten atheromatösen Plaques: Quantifizierung der Proliferationsrate von glatten Muskelzellen

Hanke, Hartmut; Oberhoff, Martin; Karsch, K. R.; Betz, E.; Strohschneider, T.

doi:10.1007/978-3-663-01946-6_25

Cited by 6 publications

(7 citation statements)

References 17 publications

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“…Maximal DNA synthesis occurred at -7 d (43) and lasted for at least 14 d. Our observations suggest a mechanism other than the inhibition of local cell replication by which to explain the inhibition of neointimal proliferation in the rabbit injury model. We demonstrate a significant decrease in VSMC migration after exposure to pS-NO-BSA which may, in part, explain these findings.…”

Section: Discussionmentioning

confidence: 60%

Inhibition of neointimal proliferation in rabbits after vascular injury by a single treatment with a protein adduct of nitric oxide.

Marks¹,

Vita²,

Folts³

et al. 1995

J. Clin. Invest.

212

108

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IntroductionEndothelium-derived relaxing factor is important for vascular homeostasis and possesses qualities that may modulate vascular injury, including vasodilation, platelet inhibition, and inhibition of smooth muscle proliferation. S-nitrososerum albumin is a naturally occurring adduct of nitric oxide (NO) with a prolonged biologic half-life and is a potent vasodilator and platelet inhibitor. Given the avidity of serum albumin for subendothelial matrix and the antiproliferative effects of NO, we investigated the effects of locally delivered S-nitroso-bovine serum albumin (S-NO-BSA) and a polythiolated form of bovine serum albumin (pS-BSA) modified to carry several S-nitrosothiol groups (pS-NO-BSA) on neointimal responses in an animal model of vascular injury.Locally delivered S-NO-BSA bound preferentially to denuded rabbit femoral vessels producing a 26-fold increase in local concentration compared with uninjured vessels (P = 0.029). pS-NO-BSA significantly reduced the intimal/medial ratio (P = 0.038) and did so in conjunction with elevations in platelet (P < 0.001) and vascular cGMP content (P < 0.001). pS-NO-BSA treatment also inhibited platelet deposition (P = 0.031) after denuding injury. Comparison of BSA, S-NO-BSA, pS-NO-BSA, and control revealed a dose-response relationship between the amount of displaceable NO delivered and the extent of inhibition of neointimal proliferation at 2 wk (P < 0.001).Local administration of a stable protein S-nitrosothiol inhibits intimal proliferation and platelet deposition after vascular arterial balloon injury. This strategy for the local delivery of a long-lived NO adduct has potential for preventing restenosis after angioplasty. (J. Clin. Invest. 1995Invest. . 96:2630Invest. -2638

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Section: Discussionmentioning

confidence: 60%

Inhibition of neointimal proliferation in rabbits after vascular injury by a single treatment with a protein adduct of nitric oxide.

Marks¹,

Vita²,

Folts³

et al. 1995

J. Clin. Invest.

212

108

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“…This result suggests that the a-thrombin-induced growth effects in rat SMC were mediated by a receptor similar or identical to the human thrombin receptor. The vascular response to balloon angioplasty is complex and involves processes other than SMC proliferation (2)(3)(4)(5). Moreover, results of cell culture experiments cannot be directly extrapolated to events in vivo.…”

Section: Resultsmentioning

confidence: 99%

“…Despite a high early success rate, restenosis occurs in -30-35% ofpatients by 6 mo ( 1 ). Smooth muscle cell (SMC)' proliferation is known to con-tribute to postangioplasty restenosis (2)(3)(4)(5), and as such there has been extensive interest in identifying the factors that modulate SMC proliferation. The vascular injury induced by angioplasty results in activation of the coagulation cascade which can generate -140 nM concentration of thrombin (6).…”

Section: Introductionmentioning

confidence: 99%

Thrombin stimulates proliferation of cultured rat aortic smooth muscle cells by a proteolytically activated receptor.

McNamara¹,

Sarembock²,

Gimple³

et al. 1993

J. Clin. Invest.

506

297

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Thrombin has been implicated in the stimulation of smooth muscle cell (SMC) proliferation that contributes to post angioplasty restenosis. The present studies demonstrated that human a-thrombin was a potent and efficacious mitogen for cultured rat aortic SMC, stimulating an increase in 3H-thymidine incorporation, as well as an increase in cell number at 1 to 10 nM concentration. -Thrombin, which is enzymatically active but lacks fibrinogen clotting activity, stimulated SMC mitogenesis but was -10-fold less potent than a-thrombin. In contrast, D-phenylalanyl-L-propyl-L-arginyl-chloromethyl ketonea-thrombin, which lacked enzymatic activity, had no mitogenic effect. Diisopropylfluorophosphate-a-thrombin failed to stimulate mitogenesis except at concentrations having equivalent enzymatic activity as that of a-thrombin at its threshold for mitogenesis. Thus, thrombin-induced proliferation was dependent on enzymatic activity. A 14-residue peptide (SFLLRNPNDKY-EPF) corresponding to amino acids 42 through 55 of the human thrombin receptor (Vu, T. K., D. T. Hung, V. I. Wheaton, and S. R. Coughlin, 1991. Cell. 64:1057-1068) had full efficacy in stimulating SMC proliferation. Reversing the first two amino acids of this peptide abolished mitogenic activity. Northern analysis demonstrated that SMC expressed a single mRNA species that hybridized to a labeled thrombin receptor cDNA probe. These findings indicate that a-thrombin stimulates SMC proliferation via the proteolytic activation of a receptor very similar or identical to that previously identified. (J. Clin. Invest. 1993. 91:94-98.)

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“…2 B), suggesting that adenoviral vectors may track along dissection planes and infect cells in deeper regions of the arterial wall. The ability to infect these layers may be of importance since cells in these regions of the media may contribute to cellular proliferation and intimal hyperplasia (22,23).…”

Section: Resultsmentioning

confidence: 99%

Regulation of cellular proliferation and intimal formation following balloon injury in atherosclerotic rabbit arteries

1997

ACC Current Journal Review

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Injury to atherosclerotic arteries induces the expression of growth regulatory genes that stimulate cellular proliferation and intimal formation. Intimal expansion has been reduced in vivo in nonatherosclerotic balloon-injured arteries by transfer of genes that inhibit cell proliferation. It is not known, however, whether vascular cell proliferation can be inhibited after injury in more extensively diseased atherosclerotic arteries. Accordingly, the purpose of this study was to investigate whether expression of recombinant genes in atherosclerotic arteries after balloon injury could inhibit intimal cell proliferation. To test this hypothesis, we examined the response to balloon injury in atherosclerotic rabbit arteries after gene transfer of herpesvirus thymidine kinase gene (

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Transluminale Angioplastie von experimentell erzeugten atheromatösen Plaques: Quantifizierung der Proliferationsrate von glatten Muskelzellen

Cited by 6 publications

References 17 publications

Inhibition of neointimal proliferation in rabbits after vascular injury by a single treatment with a protein adduct of nitric oxide.

Inhibition of neointimal proliferation in rabbits after vascular injury by a single treatment with a protein adduct of nitric oxide.

Thrombin stimulates proliferation of cultured rat aortic smooth muscle cells by a proteolytically activated receptor.

Regulation of cellular proliferation and intimal formation following balloon injury in atherosclerotic rabbit arteries

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