Kinetics of cellular proliferation after arterial injury. IV. Heparin inhibits rat smooth muscle mitogenesis and migration.

Clowes, A W; Clowes, Monika M.

doi:10.1161/01.res.58.6.839

Cited by 297 publications

(182 citation statements)

References 21 publications

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“…38 In vitro, heparin inhibits smooth muscle cell migration and proliferation. 39 Our present data also indicate that heparin-like molecules can limit intimal proliferation in response to arterial wall immune injury. The content of intimal proliferation was also modified by heparin.…”

Section: Heparin Effectssupporting

confidence: 73%

Additive and synergistic effects of a low-molecular-weight, heparin-like molecule and low doses of cyclosporin in preventing arterial graft rejection in rats.

Plissonnier

Amichot

Lecagneux

et al. 1993

Arterioscler Thromb

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Arteriosclerotic intimal proliferation is one of the main long-term complications of organ transplantation. Low-molecular-weight, heparin-like molecules prevent myointimal proliferation in arterial wall injury and limit rejection in skin allografts. Cyclosporin limits rejection but has no major effect on intimal proliferation. Therefore, an experimental protocol was designed to test whether heparin-like molecules interacted with low doses of cyclosporin to prevent arterial wall immune system injury and response in a model of arterial graft rejection in normotensive and hypertensive rats. Aortic allografts were performed in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) normotensive control rats. Four groups of 10 allografted (SHR and WKY) rats were used: one group was treated with placebo, one with low doses of cyclosporin (2 nig/kg body wt per day), one with low-molecular-weight, heparin-like molecule (1 nig/kg body wt per hour), and one with low doses of cyclosporin plus low-molecular-weight, heparin-like molecule. Ten SHRs and 10 WKYs were isografted and served as the control groups. All rats were killed 8 weeks after aortic grafting. Structural parameters of the grafted segment were measured by morphometric analysis on formalin-fixed sections with specific stains. The classical signs of immune system injury and response were present in the untreated allografts in SHRs and WKYs: inflammatory infiltration of the adventitia, medial injury, and intimal proliferative response. Low doses of cyclosporin had a significant beneficial effect on immune medial injury by increasing medial thickness and the number of remaining smooth muscle cells and decreasing the extracellular matrix injury. Cyclosporin had no protective effect on intimal proliferation. Low-molecularweight, heparin-like molecules had a beneficial effect on both the medial injury and the intimal proliferative response that was independent of blood pressure. Heparin-like molecules increased medial thickness and partially prevented smooth muscle cell loss and extracellular matrix attack. They also significantly decreased the intimal thickness by acting more on the collagen content than on the smooth muscle cell density. Low doses of cyclosporin plus heparin-like molecules had a marked effect in preventing the arterial wall injury and response. This combination resulted in a normal medial appearance, increased medial thickness and smooth muscle cell number, and no intimal proliferation or adventitial inflammation. Thus, heparin-like molecules appear to act in concert with low doses of cyclosporin in preventing rejection-induced arterial wall remodeling in an experimental model of aortic allograft in rats, and their effects are independent of blood pressure. (Arteriosclerosis and Thrombosis 1993;13:112-119)

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Section: Heparin Effectssupporting

confidence: 73%

Additive and synergistic effects of a low-molecular-weight, heparin-like molecule and low doses of cyclosporin in preventing arterial graft rejection in rats.

Plissonnier

Amichot

Lecagneux

et al. 1993

Arterioscler Thromb

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“…RNA analysis revealed significantly decreased amounts ofPCNA mRNA in the antisense oligonucleotide-treated animals as compared with The initial wave of medial smooth muscle proliferation peaks at 72 h after balloon angioplasty in the rat carotid artery injury model (18). Given the effective suppression of PCNA message at 24 h, we then investigated the action of antisense 1 PCNA oligonucleotides, as compared with sense 1 control oligonucleotides, on the first wave of medial smooth muscle cell growth.…”

Section: Resultsmentioning

confidence: 99%

Antisense proliferating cell nuclear antigen oligonucleotides inhibit intimal hyperplasia in a rat carotid artery injury model.

Simons

Edelman²,

Rosenberg³

1994

J. Clin. Invest.

111

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We have used antisense phosphorothioate oligonucleotides to define the role played by proliferating cell nuclear antigen (PCNA) in neointimal accumulation of smooth muscle cells in a rat carotid artery injury model. The short-term extraluminal delivery of 250 nmol of antisense oligonucleotides, but not control oligonucleotides, immediately after arterial injury produces a 77% suppression of PCNA mRNA after 24 h and a 52% decrease in the frequency of medial smooth muscle cells expressing PCNA after 72 h. This reduction in PCNA expression is accompanied by a 59% decrease in the frequency of proliferating medial smooth muscle cells at 3 d as measured by BudR staining and an 80% decrease in neointimal accumulation assessed morphometrically at 2 wk. Thus, the expression of PCNA is required for medial smooth muscle cell growth in vivo and for neointimal formation after arterial injury. (J. Clin. Invest. 1994Invest. . 93:2351Invest. -2356

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“…Heparin also is effective in reducing smooth muscle cell proliferation in vivo after arterial injury and is thus capable of counteracting the effects of local and blood borne growth factors. 169 Associated with this cessation of growth is an increase in the concentration of proteoglycans in injured arteries. 170 In vitro studies have also shown that arterial smooth muscle cell cultures accumulate more proteoglycan in the presence of heparin.…”

mentioning

confidence: 99%

Cell biology of arterial proteoglycans.

1989

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Kinetics of cellular proliferation after arterial injury. IV. Heparin inhibits rat smooth muscle mitogenesis and migration.

Cited by 297 publications

References 21 publications

Additive and synergistic effects of a low-molecular-weight, heparin-like molecule and low doses of cyclosporin in preventing arterial graft rejection in rats.

Additive and synergistic effects of a low-molecular-weight, heparin-like molecule and low doses of cyclosporin in preventing arterial graft rejection in rats.

Antisense proliferating cell nuclear antigen oligonucleotides inhibit intimal hyperplasia in a rat carotid artery injury model.

Cell biology of arterial proteoglycans.

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