Nitric Oxide Reversibly Inhibits the Migration of Cultured Vascular Smooth Muscle Cells

Abstract

Augmentation of nitric oxide (NO) production in vivo decreases lesions in a variety of models of arterial injury, and inhibition of NO synthase exacerbates experimental intimal lesions. Both vascular smooth muscle cell (VSMC) proliferation and migration contribute to lesion formation. Although NO inhibits VSMC proliferation, its effects on VSMC migration are unknown. To test the hypothesis that NO inhibits VSMC migration independent of inhibition of proliferation, we examined migration of rat aortic VSMCs after wounding of a confluent culture in the presence of chemical donors of NO. Hydroxyurea was used to eliminate any confounding effect of NO on proliferation. Three NO donors, diethylamine NONOate, spermine NONOate, and S-nitrosoglutathione, exhibited concentration-dependent inhibition of both number of migrating VSMCs and maximal distance migrated. Inhibition of migration was also seen with 8-Br-cGMP, suggesting that activation of guanylate cyclase may play a role in mediating the antimigratory effects of NO. Migration resumed after removal of NO donors, as evidenced by an increase in distance migrated. Measurement of VSMC protein synthesis and mitochondrial respiration indicated that inhibition of migration by NO donors was not due to metabolic cytostasis. These findings indicate that NO reversibly inhibits VSMC migration independent of proliferation or cytotoxicity, a novel mechanism by which both endogenous and pharmacological NO may alter vascular pathology.

Stromal Cell-Derived Factor 1α-Induced Chemotaxis in T Cells Is Mediated by Nitric Oxide Signaling Pathways

“…NO has been shown to have opposing and complex effects on chemotactic responses exerted by various stimuli. For example, it has been shown that NO enhances chemotactic responses in some cell types (45,46,(61)(62)(63) upon certain stimuli, while inhibiting cell migration in others (47,64). Furthermore, NO has been shown to modulate T cell chemotaxis in Peyer's patches and in the nonlymphoid region of the intestine (65).…”

“…Although NO can regulate migration in several cell types (45)(46)(47)(48), its role in chemokine-mediated chemotaxis in T cells is not known. We now report that SDF1␣ treatment activates NOS in Jurkat T cells.…”

Nitrovasodilators inhibit platelet-derived growth factor-induced proliferation and migration of activated human hepatic stellate cells

“…26 In addition, a possible direct antifibrogenic effect of NO donors is suggested by in vitro studies showing antiproliferative and antichemotactic actions of these compounds in vascular smooth muscle cells and glomerular mesangial cells. [27][28][29][30] However, the possible cellular and molecular mechanisms responsible for the action of NO donors in this setting have not been clarified.…”

The role of Src homology 2 containing protein tyrosine phosphatase 2 in vascular smooth muscle cell migration and proliferation

“…This raises the question regarding the precise nature of the Gab1/VAV interaction in proliferation and migration. When VSMCs are dedifferentiated, NO is capable of reducing motility [38] and blocking the increased motility in response to PDGF treatment. However, after an extended period of culture in dedifferentiated cells with insulin, a Gab1/SHP2 interaction may lead to a decrease in Rho A abundance en route to the increased motility [39] .…”