Effect of the Direct Nitric Oxide Donors Linsidomine and Molsidomine on Angiographic Restenosis After Coronary Balloon Angioplasty

Lablanche, Jean‐Marc; Grollier, Gilles; Lusson, Jean-René; Bassand, Jean‐Pierre; Drobinski, Ge ́rard; Bertrand, Bernard; Battaglia, Salvatore; Desveaux, B; Juillière, Yves; Juliard, Jean‐Michel; Metzger, J; Coste, Pierre; Quiret, J C; Dubois‐Randé, Jean‐Luc; Crochet, Pierre Dominique; Letac, B; Boschat, J; Virot, P; Finet, G; Breton, Hervé; Livarek, B.; Leclercq, Florence; ́ard, Thierry Be; Giraud, T; McFadden, Eugène; Bertrand, Michel E.

doi:10.1161/01.cir.95.1.83

Cited by 97 publications

(46 citation statements)

References 34 publications

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“…Recently, the ACCORD study showed that in patients with atherosclerotic heart disease undergoing angioplasty, shortterm treatment with NO donors (12 to 24 hours) was associated with a modest improvement in immediate angiographic result, which was sustained at 6-month angiographic follow-up. 23 Systemic administration of NO donors may, however, be associated with hypotensive side effects, especially when high local concentrations in the vessel wall are desired. Moreover, these pharmacological studies did not distinguish between effects on SMC migration and/or proliferation or on the adhesion of circulating leukocytes or platelets with release of growth factors and mitogens.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…It is therefore tempting to speculate that the mechanisms outlined in the present investigation may play a role in hyperinsulinemic states in vivo by reducing or even reversing the protective effect of NO in vascular remodeling. Also of note, studies (18,32) of the effects of NO in patients undergoing angioplasty found no significant decrease of neointimal expansion, perhaps related to the concomitantly high levels of insulin expected to occur in this cohort and the cell signaling pathways outlined in the present report.…”

Section: Discussionmentioning

confidence: 47%

Mechanisms related to NO-induced motility in differentiated rat aortic smooth muscle cells

Zhuang

Thakur

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Pu Q, Zhuang D, Thakran S, Hassid A. Mechanisms related to NO-induced motility in differentiated rat aortic smooth muscle cells. Am J Physiol Heart Circ Physiol 300: H101-H108, 2011. First published October 29, 2010 doi:10.1152/ajpheart.00342.2010 is thought to play an important role as an inhibitor of vascular cell proliferation, motility, and neointima formation. This effect is mediated, in part, via the upregulation of protein tyrosine phosphatase (PTP)1B. Conversely, studies have reported that in presumably hyperinsulinemic mice fed a high-fat diet, NO enhances vascular remodeling, whereas a deficit of NO attenuates vascular remodeling. We have reported that in differentiated cultured smooth muscle cells treated with insulin, NO induces a motogenic effect that is dependent on Src homology-2 domain PTP 2 (SHP2) upregulation. In the present study, we describe novel mechanisms relevant to the motogenic effect of NO. Treatment of cultured cells with the selective angiontensin type 1 receptor antagonist losartan, but not with the selective angiotensin type 2 receptor antagonist PD-123319, blocked the comotogenic capacity of NO and insulin. Insulin and NO increased the secretion of ANG II into the culture media by 2-and 2.5-fold (P Ͻ 0.05), respectively, whereas treatment of cells with ANG II uncovered the motogenic effect of NO (1.4-fold above control, P Ͻ 0.05) and decreased the levels of PTP1B to 45% of control (P Ͻ 0.05). Suppression of PTP1B function was sufficient to uncover the motogenic effect of NO. The capacity of insulin to suppress PTP1B activity was blocked by losartan, implicating ANG II function in mediating this effect. Both insulin and ANG II induced the upregulation of phosphatidyl inositol 3-kinase (PI3K)-␦ by two-to threefold (P Ͻ 0.05), and this effect was both necessary and sufficient to uncover NO-induced motogenesis. Finally, suppression of PTP1B function potentiated, whereas overexpression of PTP1B inhibited, SHP2-induced motogenesis. These results support the hypothesis that the comotogenic effect of insulin and NO occurs via an ANG II-mediated effect involving the suppression of PTP1B and upregulation of PI3K-␦ and SHP2. nitric oxide; vascular smooth muscle; angiotensin II; protein tyrosine phosphatases NITRIC OXIDE (NO) is generally thought to attenuate vascular remodeling, and numerous studies have reported that it decreases neointima formation and atherosclerosis in models of vascular injury. In vivo, inducible NO synthase (iNOS) levels have been reported to be increased in medial cells, almost immediately after vascular injury, and subsequently in neointimal cells (12,34). Inducible NO levels are also increased in diabetes. Several groups, including ours, have reported that NO donors decrease aortic smooth muscle cell motility and proliferation in culture (11,24,26). Moreover, many in vivo studies have shown that exogenous or endogenous NO attenuates neointima formation induced by vascular injury, consistent with the overall inhibition of vascular smooth muscle cell motility and pro...

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“…Consistent with these concepts are the results of the ACCORD study, which recently demonstrated that treating angioplasty patients for 12-24 h with NO donors results in a modest improvement in immediate and 6-month angiographic results. 30 Therefore, more information about the role of the endothelium and vasa vasorum in diseased arteries is needed in order to better understand both lesion development and adaptive changes in arterial wall dimensions.…”

Section: Discussionmentioning

confidence: 99%

Abundance of Plaque Microvessels is Associated With Constrictive Remodeling in Angioplastied Human Coronary Arteries.

et al. 2001

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Effect of the Direct Nitric Oxide Donors Linsidomine and Molsidomine on Angiographic Restenosis After Coronary Balloon Angioplasty

Cited by 97 publications

References 34 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

Mechanisms related to NO-induced motility in differentiated rat aortic smooth muscle cells

Abundance of Plaque Microvessels is Associated With Constrictive Remodeling in Angioplastied Human Coronary Arteries.

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