Nitric Oxide and C-Type Atrial Natriuretic Peptide Stimulate Primary Aortic Smooth Muscle Cell Migration via a cGMP-Dependent Mechanism

Brown, Claire M.; Pan, Xiaolei; Hassid, Aviv

doi:10.1161/01.res.84.6.655

Cited by 78 publications

(84 citation statements)

References 55 publications

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“…12 We did not use ODQ with noninduced cells because insulin did not affect cGMP production or migration in those cells, and it has been reported that ODQ per se does not affect VSMC migration. 17 These data indicate that the inhibition by insulin of the migration of induced VSMCs is dependent on the stimulation by the hormone of cGMP production. The findings that, in the absence of insulin, cells with iNOS have increased basal cGMP levels and lower migration rates compared with noninduced cells indicate that basal cGMP production induced by iNOS-derived NO inhibited the migration of these VSMCs.…”

Section: Discussionmentioning

confidence: 84%

Insulin Inhibits Migration of Vascular Smooth Muscle Cells With Inducible Nitric Oxide Synthase

et al. 2000

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Abstract-Vascular smooth muscle cell (VSMC) migration participates in atherosclerosis and arterial restenosis after balloon angioplasty. Because these processes are enhanced in insulin-resistant states, our goal was to determine whether insulin affects VSMC migration and, if so, how. The migration of primary cultured VSMCs from canine femoral artery was measured with the use of a wound migration assay and related to cGMP levels. Insulin (1 nmol/L) did not affect migration or cGMP production in control cells. When inducible nitric oxide synthase (iNOS) was induced by 24-hour preincubation with lipopolysaccharide and interleuken-1␤, basal migration decreased, cGMP production increased, and insulin inhibited migration by Ͼ90% and stimulated cGMP production by 3-fold. The nitric oxide synthase inhibitor N G -monomethyl-L-arginine blocked the affect of insulin on the migration of VSMCs with iNOS. 8-Bromo-cGMP inhibited VSMC migration in control cells, and 1-H-1[1,2,4]oxadiazolo- [4,3a]quinoxolin-1-one, a selective inhibitor of guanylate cyclase, blocked the inhibition by insulin of migration of cells with iNOS. We conclude that insulin does not normally affect cGMP production or the migration of these VSMCs. However, after the induction of iNOS, insulin stimulates cGMP production and inhibits migration via an NOS-and a cGMP-dependent mechanism. (Hypertension. 2000;35[part 2]:303-306.)Key Words: cyclic 3Ј,5Јguanosine monophosphate Ⅲ muscle, smooth, vascular Ⅲ nitric oxide Ⅲ insulin I nsulin resistance, which occurs in obesity, non-insulindependent diabetes mellitus, and essential hypertension, is associated with increased atherosclerosis and restenosis after balloon angioplasty, 1-3 but the reasons for this are obscure. The migration of vascular smooth muscle cells (VSMCs) from the arterial media through the internal elastic membrane into the neointima is an integral part of the pathogenesis of atherosclerosis and restenosis. 4 The insulin-resistant conditions noted are marked by hyperinsulinemia as the pancreas attempts to maintain plasma glucose concentration at a normal level. 1 Because hyperinsulinemia has been thought to aggravate atherosclerosis or restenosis, 5 several investigators have studied the effects of insulin on VSMC migration. 6 -8 Although some studies have shown a small stimulation of VSMC migration with insulin, the results are controversial. In some studies, the concentrations of insulin that were used were supraphysiological, 8 such that the insulin-like growth factor-1 pathway may have been activated. Insulin-like growth factor-1 is known to stimulate VSMC migration. 9 In other studies, insulin alone had no effect on VSMC migration 6 but increased it when it was stimulated by another agent. 7 We have reported that physiological concentrations of insulin stimulated cGMP production in primary cultured VSMCs from canine femoral artery. 10,11 These cells were cultured under conditions such that they expressed the inducible isoform of nitric oxide synthase (iNOS), 11 and an inhibitor of NOS blocked ...

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Section: Discussionmentioning

confidence: 84%

Insulin Inhibits Migration of Vascular Smooth Muscle Cells With Inducible Nitric Oxide Synthase

et al. 2000

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“…25,39 This difference appears to be correlated with the different cytoskeletal phenotypes of the 2 cell types, inasmuch as cells isolated from newborn rats express a phenotype less differentiated than that of cells isolated from adult rats. 15 Moreover, the motility stimulatory effect of NO appears to require another nonmembrane protein tyrosine phosphatase, SHP2, 39 as opposed to the present results, which implicate PTP1B as an inhibitor of cell motility.…”

Section: July 2002mentioning

confidence: 99%

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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“…Thus, the improved wound healing by this compound was likely a result of cells migrating into the wounded area. Other studies have also shown that NO increases cell migration, but it can also inhibit motility, depending on the type of cell, level and duration of NO exposure, and assay conditions [44][45][46][47][48][49][50][51].…”

Section: Discussionmentioning

confidence: 97%

Nitrosyl-cobinamide (NO-Cbi), a new nitric oxide donor, improves wound healing through cGMP/cGMP-dependent protein kinase

Spitler

Schwappacher

et al. 2013

Cellular Signalling

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a b s t r a c t a r t i c l e i n f oNitric oxide (NO) donors have been shown to improve wound healing, but the mechanism is not well defined. Here we show that the novel NO donor nitrosyl-cobinamide (NO-Cbi) improved in vitro wound healing in several cell types, including an established line of lung epithelial cells and primary human lung fibroblasts. On a molar basis, NO-Cbi was more effective than two other NO donors, with the effective NO-Cbi concentration ranging from 3 to 10 μM, depending on the cell type. Improved wound healing was secondary to increased cell migration and not cell proliferation. The wound healing effect of NO-Cbi was mediated by cGMP, mainly through cGMPdependent protein kinase type I (PKGI), as determined using pharmacological inhibitors and activators, and siRNAs targeting PKG type I and II. Moreover, we found that Src and ERK were two downstream mediators of NO-Cbi's effect. We conclude that NO-Cbi is a potent inducer of cell migration and wound closure, acting via cGMP, PKG, Src, and extracellular signal regulated kinase (ERK).

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Nitric Oxide and C-Type Atrial Natriuretic Peptide Stimulate Primary Aortic Smooth Muscle Cell Migration via a cGMP-Dependent Mechanism

Cited by 78 publications

References 55 publications

Insulin Inhibits Migration of Vascular Smooth Muscle Cells With Inducible Nitric Oxide Synthase

Insulin Inhibits Migration of Vascular Smooth Muscle Cells With Inducible Nitric Oxide Synthase

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

Nitrosyl-cobinamide (NO-Cbi), a new nitric oxide donor, improves wound healing through cGMP/cGMP-dependent protein kinase

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