Rho-GDP dissociation inhibitor alpha downregulated by low shear stress promotes vascular smooth muscle cell migration and apoptosis: a proteomic analysis

Qi, Ying‐Xin; Qu, Mingjuan; Long, Ding-Kun; Liu, Bo; Yao, Qing; Chien, Shu; Jiang, Zong‐Lai

doi:10.1093/cvr/cvn158

Cited by 73 publications

(68 citation statements)

References 34 publications

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“…On the contrary, the low shear stress induces VSMC proliferation [20,23]. Similar results are also observed in tissue culture studies [24][25][26][27], hence the low shear stress may act as a critical factor for intimal hyperplasia. Subnormal shear-stress-induced intimal thickening requires VSMC proliferation and migration [28], and it is well known that the mechanism of VSMC proliferation and migration regulated by shear stress involves platelet-derived growth factor (PDGF) [29] and matrix metalloproteinase-2 (MMP-2) through nitric oxide (NO) signalling pathway [30,31].…”

Section: Haemodynamic Factors and Vascular Smoothsupporting

confidence: 62%

Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding

Qiu

Zheng

et al. 2014

J. R. Soc. Interface.

149

115

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Vascular smooth muscle cells (VSMCs) have critical functions in vascular diseases. Haemodynamic factors are important regulators of VSMC functions in vascular pathophysiology. VSMCs are physiologically active in the threedimensional matrix and interact with the shear stress sensor of endothelial cells (ECs). The purpose of this review is to illustrate how haemodynamic factors regulate VSMC functions under two-dimensional conditions in vitro or three-dimensional co-culture conditions in vivo. Recent advances show that high shear stress induces VSMC apoptosis through endothelial-released nitric oxide and low shear stress upregulates VSMC proliferation and migration through platelet-derived growth factor released by ECs. This differential regulation emphasizes the need to construct more actual environments for future research on vascular diseases (such as atherosclerosis and hypertension) and cardiovascular tissue engineering.

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Section: Haemodynamic Factors and Vascular Smoothsupporting

confidence: 62%

Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding

Qiu

Zheng

et al. 2014

J. R. Soc. Interface.

149

115

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“…Boulter et al recently described how GDI␣ depletion triggers degradation of Rho proteins and modifies melanoma cell migration (4). Qi et al also described how the simple reduction of GDI␣ expression can induce Rac1 activation and VSMC migration (35). These works and the present study highlight how GDFs are determinants of cell physiology.…”

Section: Discussionsupporting

confidence: 77%

RhoA Phosphorylation Induces Rac1 Release from Guanine Dissociation Inhibitor α and Stimulation of Vascular Smooth Muscle Cell Migration

Rolli–Derkinderen

Toumaniantz

Pacaud

et al. 2010

Molecular and Cellular Biology

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Although overactivation of RhoA is recognized as a common component of vascular disorders, the molecular mechanisms regulating RhoA activity in vascular smooth muscle cells (VSMC) are still unclear. We have previously shown that in VSMC, RhoA is phosphorylated on Ser188 by nitric oxide (NO)-stimulated cGMPdependent kinase (PKG), which leads to RhoA-Rho kinase pathway inhibition. In this study, we showed that expression of phosphoresistant RhoA mutants prevented the stimulation of VSMC migration and adhesion induced by NO-PKG pathway activation. In contrast, under basal conditions, phosphomimetic RhoA mutants stimulated VSMC adhesion and migration through a signaling pathway requiring Rac1 and the Rho exchange factor Vav3. RhoA phosphorylation or phosphomimetic RhoA mutants induced Rac1 activation but did not activate Vav3. Indeed, phosphorylated RhoA or phosphomimetic mutants trapped guanine dissociation inhibitor ␣ (GDI␣), leading to the release of Rac1 and its translocation to the membrane, where it was then activated by the basal Vav3 nucleotide exchange activity. In vivo, RhoA phosphorylation induced by PKG activation in the aortas of rats treated with sildenafil induced dissociation of Rac1 from GDI␣ and activation of the Rac1 signaling pathway. These results suggest that the phosphorylation of RhoA represents a novel potent and physiological GDI␣ displacement factor that leads to Rac1 activation and regulation of Rac1-dependent VSMC functions.

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“…There were 43 protein spots differentially expressed between NSS and LowSS cultured vessels (Table S1), among which eight proteins were highly expressed in vessels under NSS and 35 proteins were highly expressed in LowSS. Rho dissociation factor α, which was shown to regulate VSMC migration and apoptosis in our previous study (13), did show a lower expression in LowSS in the current study (Table S1), but was not included in the IPArevealed signaling network because it did not pass the significance level of P < 0.05 ( Fig. 2 and Table S2).…”

Section: Resultsmentioning

confidence: 67%

“…Growing evidence, both in vivo and in vitro, has revealed that the essential pathology of vascular remodeling during atherosclerosis induced by low and oscillating shear stresses involves the proliferation, apoptosis, migration, and phenotype transformation of VSMCs (2,13,14). As ECs are directly exposed to shear stress, understanding of their crosstalk with VSMCs under shear flow can help to elucidate the molecular mechanism of the vascular remodeling induced by low shear stress (LowSS).…”

mentioning

confidence: 99%

PDGF-BB and TGF-β1 on cross-talk between endothelial and smooth muscle cells in vascular remodeling induced by low shear stress

Jiang

et al. 2011

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

Self Cite

148

112

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Shear stress, especially low shear stress (LowSS), plays an important role in vascular remodeling during atherosclerosis. Endothelial cells (ECs), which are directly exposed to shear stress, convert mechanical stimuli into intracellular signals and interact with the underlying vascular smooth muscle cells (VSMCs). The interactions between ECs and VSMCs modulate the LowSS-induced vascular remodeling. With the use of proteomic analysis, the protein profiles of rat aorta cultured under LowSS (5 dyn/cm 2 ) and normal shear stress (15 dyn/cm 2 ) were compared. By using Ingenuity Pathway Analysis to identify protein–protein association, a network was disclosed that involves two secretary molecules, PDGF-BB and TGF-β1, and three other linked proteins, lamin A, lysyl oxidase, and ERK 1/2. The roles of this network in cellular communication, migration, and proliferation were further studied in vitro by a cocultured parallel-plate flow chamber system. LowSS up-regulated migration and proliferation of ECs and VSMCs, increased productions of PDGF-BB and TGF-β1, enhanced expressions of lysyl oxidase and phospho-ERK1/2, and decreased Lamin A in ECs and VSMCs. These changes induced by LowSS were confirmed by using PDGF-BB recombinant protein, siRNA, and neutralizing antibody. TGF-β1 had similar influences on ECs as PDGF-BB, but not on VSMCs. Our results suggest that ECs convert the LowSS stimuli into up-regulations of PDGF-BB and TGF-β1, but these two factors play different roles in LowSS-induced vascular remodeling. PDGF-BB is involved in the paracrine control of VSMCs by ECs, whereas TGF-β1 participates in the feedback control from VSMCs to ECs.

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Rho-GDP dissociation inhibitor alpha downregulated by low shear stress promotes vascular smooth muscle cell migration and apoptosis: a proteomic analysis

Abstract: The results indicate that the LSS-induced VSMC migration and apoptosis are mediated by a downregulation of Rho-GDIalpha. The effect of Rho-GDIalpha on VSMC migration is mediated by the PI3K/Akt pathway, but its effect on VSMC apoptosis is not.

Cited by 73 publications

References 34 publications

Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding

Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding

RhoA Phosphorylation Induces Rac1 Release from Guanine Dissociation Inhibitor α and Stimulation of Vascular Smooth Muscle Cell Migration

PDGF-BB and TGF-β1 on cross-talk between endothelial and smooth muscle cells in vascular remodeling induced by low shear stress

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