L-Arginine Inhibits Balloon Catheter-Induced Intimal Hyperplasia

McNamara, Dennis B.; Bedi, Brenda; Aurora, Harmeet; Tena, L.; Ignarro, Louis J.; Kadowitz, Philip J.; Akers, Donald L.

doi:10.1006/bbrc.1993.1622

Cited by 220 publications

(102 citation statements)

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“…11,12 Furthermore, several studies in vivo have reported that NO, or its precursor arginine, attenuates neointima formation after experimental vascular injury. 13,14 These findings are consistent with the capacity of NO to decrease smooth muscle cell motility in culture, at least in cells expressing a relatively dedifferentiated cytoskeletal phenotype, as found in cultured cells from newborn rats. 15 Of further relevance is the finding that type II diabetes may be associated with a deficit of NO; moreover, amelioration of the consequences of hyperinsulinemia by NO has also been reported.…”

supporting

confidence: 84%

NO Attenuates Insulin Signaling and Motility in Aortic Smooth Muscle Cells via Protein Tyrosine Phosphatase 1B–Mediated Mechanism

Nair

Yan

Hassid

2002

ATVB

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Objective-Hyperinsulinemia is a significant risk factor for the pathogenesis of vascular disease. Protein tyrosine phosphatase 1B (PTP1B) has been recognized as a modulator of insulin signaling in nonvascular cells, and we have recently reported that NO increases the activity of PTP1B in rat vascular smooth muscle cells. In the present study, we tested the hypothesis that NO attenuates insulin-stimulated cell motility via a PTP1B-mediated mechanism involving downregulation of insulin signal transduction. Methods and Results-Treatment of primary aortic smooth muscle cells from newborn rats with the NO donor S-nitroso-N-acetylpenicillamine reduced cell motility, tyrosine phosphorylation levels of insulin receptor ␤ subunit and insulin receptor substrate-1, and extracellular signal-regulated kinase activity. Overexpression of wild-type PTP1B via an adenoviral vector blocked the capacity of insulin to stimulate cell motility and insulin receptor phosphorylation, whereas expression of a dominant-negative mutant of PTP1B attenuated the capacity of NO to decrease cell motility. Conclusions-Our findings indicate that activation of PTP1B is necessary and sufficient to account for the capacity of NO to decrease insulin-stimulated signal transduction and cell motility in cultured aortic smooth muscle cells. The results could explain the capacity of NO to oppose neointima formation in states of hyperinsulinemia. Key Words: cell signaling Ⅲ signal transduction Ⅲ atherosclerosis Ⅲ growth factors Ⅲ type 2 diabetes T ype II diabetes is a major risk factor for the pathogenesis of vascular disease, including that associated with hypertension and atherosclerosis. That diabetes increases the frequency of coronary vessel restenosis occurring after angioplasty is also well established. 1 Most forms of vascular disease in conduit arteries manifest neointimal enlargement, and although type II diabetes is associated with hyperglycemia as well as hyperinsulinemia, recent studies have suggested that elevated insulin levels may be the more important factor in the pathogenesis of neointimal enlargement. 2,3 The proliferation and motility of vascular smooth muscle cells is regulated in reciprocal fashion by stimulators (eg, fibroblast growth factor, platelet-derived growth factor, and heparin-binding epidermal growth factor) and inhibitors of mitogenesis or motility (eg, prostanoids, heparin, atrial natriuretic factor, and transforming growth factor-␤). 4 -7 Similar to many other growth factors, insulin has the capacity to stimulate cell motility in vitro, which could explain the pathogenesis of diabetic neointimal growth. 3,8 Early studies from several laboratories, including ours, have reported that NO decreases vascular smooth muscle cell proliferation in subcultured cells from adult rats or in primary cultures from newborn rats. 9,10 More recent studies have reported that NO also inhibits aortic smooth muscle cell motility. 11,12 Furthermore, several studies in vivo have reported that NO, or its precursor arginine, attenuates neointima ...

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supporting

confidence: 84%

NO Attenuates Insulin Signaling and Motility in Aortic Smooth Muscle Cells via Protein Tyrosine Phosphatase 1B–Mediated Mechanism

Nair

Yan

Hassid

2002

ATVB

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“…This effect on smooth muscle may seem counterintuitive. It has been long known that NO inhibits smooth muscle proliferation with evidence of this effect both in vitro (31) and in vivo (32), and that nitrite also exerts inhibitory effects on proliferation in a vascular injury model (33). We propose that the accumulation of smooth muscle within the plaque is likely an indirect effect of reduced macrophage content.…”

Section: Discussionmentioning

confidence: 77%

Antiinflammatory actions of inorganic nitrate stabilize the atherosclerotic plaque

Khambata

Ghosh

Rathod

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Reduced bioavailable nitric oxide (NO) plays a key role in the enhanced leukocyte recruitment reflective of systemic inflammation thought to precede and underlie atherosclerotic plaque formation and instability. Recent evidence demonstrates that inorganic nitrate (NO 3 − ) through sequential chemical reduction in vivo provides a source of NO that exerts beneficial effects upon the cardiovascular system, including reductions in inflammatory responses. We tested whether the antiinflammatory effects of inorganic nitrate might prove useful in ameliorating atherosclerotic disease in Apolipoprotein (Apo)E knockout (KO) mice. We show that dietary nitrate treatment, although having no effect upon total plaque area, caused a reduction in macrophage accumulation and an elevation in smooth muscle accumulation within atherosclerotic plaques of ApoE KO mice, suggesting plaque stabilization. We also show that in nitratefed mice there is reduced systemic leukocyte rolling and adherence, circulating neutrophil numbers, neutrophil CD11b expression, and myeloperoxidase activity compared with wild-type littermates. Moreover, we show in both the ApoE KO mice and using an acute model of inflammation that this effect upon neutrophils results in consequent reductions in inflammatory monocyte expression that is associated with elevations of the antiinflammatory cytokine interleukin (IL)-10. In summary, we demonstrate that inorganic nitrate suppresses acute and chronic inflammation by targeting neutrophil recruitment and that this effect, at least in part, results in consequent reductions in the inflammatory status of atheromatous plaque, and suggest that this effect may have clinical utility in the prophylaxis of inflammatory atherosclerotic disease.

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“…Previous studies have augmented NO levels, however, these alternative means of NO supplementation have not made it to the clinical arena due to several limitations. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]35] Systemic administration of NO is rapidly inactivated by hemoglobin in the circulating blood resulting in limited bioavailability. To overcome this limitation, larger doses of the NO donor must be administered systemically; however, these larger doses can produce adverse systemic hemodynamic and hemostatic effects, thereby precluding administration of biologically effective doses of NO.…”

Section: Discussionmentioning

confidence: 99%

“…This has been demonstrated in numerous animal models which have utilized varying NO delivery methods including inhalational NO, delivery of the substrate L-arginine, delivery of NO-donors systemically or locally, gene therapy with endothelial NO synthase (eNOS) or inducible NO synthase (iNOS), and polymer-based approaches of NO-donor delivery. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] All of these therapies have demonstrated varying degrees of success, yet none have been used in the clinical arena due to significant side effects, safety concerns, complexity of administration and, sometimes, lack of significant and durable effect.…”

Section: Introductionmentioning

confidence: 99%

Beneficial effect of a short-acting NO donor for the prevention of neointimal hyperplasia

Pearce

Najjar

Kapadia

et al. 2008

Free Radical Biology and Medicine

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Nitric oxide (NO)-based therapies effectively inhibit neointimal hyperplasia in animal models of arterial injury and bypass grafting, but are not available clinically. We created a simple, effective, locally-applied NO-eluting therapy to prevent restenosis following vascular procedures. We investigated the efficacy of perivascular delivery of two different distinctly different diazeniumdiolate NO donors, 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/ NO), (short half-life) and diazeniumdiolated poly(acrylonitrile) (PAN/NO), (long half-life), in powder or gel form (30% poloxamer 407), at inhibiting neointimal hyperplasia using the rat carotid artery injury model. Two weeks post-injury, all of the NO-eluting therapies successfully reduced neointimal hyperplasia. However, most dramatically, PROLI/NO powder reduced intimal area by 91.2% (P<0.05) versus injury alone. PROLI/NO powder was noted to reduce the medial area (40.2% vs. injury alone, P<0.05), while other groups showed no such effect. Three days post-injury, each NO treatment group significantly reduced cellular proliferation. However, inflammatory markers revealed a distinct pattern: PAN/NO groups displayed increased leukocyte infiltration (P<0.05) whereas PROLI/NO groups displayed less macrophage infiltration (P<0.05). In conclusion, perivascular delivery of diazeniumdiolate NO donors in powder or gel form effectively inhibits neointimal hyperplasia. Application of short-acting PROLI/NO powder most effectively inhibited neointimal hyperplasia and inflammation and may represent a simple, clinically applicable NOeluting therapy to prevent neointimal hyperplasia and restenosis following open vascular interventions.

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L-Arginine Inhibits Balloon Catheter-Induced Intimal Hyperplasia

Cited by 220 publications

References 0 publications

NO Attenuates Insulin Signaling and Motility in Aortic Smooth Muscle Cells via Protein Tyrosine Phosphatase 1B–Mediated Mechanism

NO Attenuates Insulin Signaling and Motility in Aortic Smooth Muscle Cells via Protein Tyrosine Phosphatase 1B–Mediated Mechanism

Antiinflammatory actions of inorganic nitrate stabilize the atherosclerotic plaque

Beneficial effect of a short-acting NO donor for the prevention of neointimal hyperplasia

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