Control of smooth muscle cell proliferation in vascular disease

Hedin, Ulf; Roy, Joy; Tran, Phan‐Kiet

doi:10.1097/00041433-200410000-00010

Cited by 74 publications

(65 citation statements)

References 61 publications

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“…This study demonstrates that platonin, a trithiazole pentamethine cyanine, inhibits PDGF-BB-stimulated VSMC prolifera- Therefore, the modulation of VSMC proliferation has important therapeutic implications [1] . In the present study, we found that platonin inhibited cell proliferation in PDGF-BBstimulated VSMCs at 1-5 µmol/L.…”

Section: Discussionmentioning

confidence: 83%

“…Abnormal proliferation of vascular smooth muscle cells (VSMCs) is implicated in the pathogenesis of several diseases, including atherosclerosis, restenosis after angioplasty, transplant vasculopathy, and failure of vein graft bypasses [1] . Numerous growth factors and cytokines are reported to be released in human vascular lesions by dysfunctional endothelial cells, inflammatory cells, platelets, and VSMCs, and these mediate chemoattraction, cell migration, proliferation, apoptosis, and matrix modulation [2] .…”

Section: Introductionmentioning

confidence: 99%

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Platonin inhibited PDGF-BB-induced proliferation of rat vascular smooth muscle cells via JNK1/2-dependent signaling

Chang

Uen²,

Chen

et al. 2011

Acta Pharmacol Sin

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Aim: To examine the inhibitory actions of the immunoregulator platonin against proliferation of rat vascular smooth muscle cells (VSMCs). Methods: VSMCs were prepared from the thoracic aortas of male Wistar rats. Cell proliferation was examined using MTT assays. Cell cycles were analyzed using flow cytometry. c-Jun N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, AKT, and c-Jun phosphorylation or p27 expression were detected using immunoblotting. Results: Pretreatment with platonin (1-5 μmol/L) significantly suppressed VSMC proliferation stimulated by PDGF-BB (10 ng/mL) or 10% fetal bovine serum (FBS), and arrested cell cycle progression in the S and G 2 /M phases. The same concentrations of platonin significantly inhibited the phosphorylation of JNK1/2 but not ERK1/2 or AKT in VSMCs stimulated by PDGF-BB. Furthermore, platonin also attenuated c-Jun phosphorylation and markedly reversed the down-regulation of p27 expression after PDGF-BB stimulation. Conclusion: Platonin inhibited VSMC proliferation, possibly via inhibiting phosphorylation of JNK1/2 and c-Jun, and reversal of p27 down-regulation, thereby leading to cell cycle arrest at the S and G 2 /M phases. Thus, platonin may represent a novel approach for lowering the risk of abnormal VSMC proliferation and related vascular diseases.

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Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Platonin inhibited PDGF-BB-induced proliferation of rat vascular smooth muscle cells via JNK1/2-dependent signaling

Chang

Uen²,

Chen

et al. 2011

Acta Pharmacol Sin

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“…induces expression of chemokines and recruitment of immune cells [9][10][11], increases expression of adhesion molecules such as vascular cell adhesion molecule 1(VCAM-1) [12]. and stimulates VSMC migration or proliferation [13]. Of these processes, there is increasing evidence that activation of inflammatory responses as a result of leukocytic infiltration and stimulation of macrophage function are necessary for lesion development and tissue remodeling [14].…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II induces IL-6 expression and the Jak-STAT3 pathway in aortic adventitia of LDL receptor-deficient mice

et al. 2007

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Angiotensin II (A-II), the major effector peptide of the renin angiotensin system potently accelerates progression of atherosclerosis. To investigate its effects on vascular inflammatory mechanisms, we elucidated vascular cytokine expression during early lesion development in A-II-infused atherosclerosis-prone LDLR −/− mice. Male LDLR −/− mice were placed on a "Western" high-fat diet for 4 weeks, followed by sham or A-II infusion for 7 weeks. Equal blood pressures and elevations in serum lipids were seen in both groups. Mice were sacrificed when significant AII-induced plaque development was first detectable, aortae were explanted and culture media assayed for secreted cytokines. Nine cytokines were significantly induced with interleukin-6 (IL-6) being the most highly secreted. Local IL-6 production was confirmed by in situ mRNA hybridization and immunostaining, where the most abundant IL-6 was found in the aortic adventitia, with lesser production by the medial and intimal layers. Immunofluorescence colocalization showed IL-6 expression by fibroblasts and activated macrophages. Activation of downstream IL-6 signaling mediated by the Jak-STAT3 pathway was demonstrated by inducible phospho-Tyr 705 -STAT3 formation in the adventitia and endothelium (of IL-6 +/+ mice only). These findings define cytokine profiles in the A-II infusion model and demonstrate that IL-6, produced by activated macrophages and fibroblasts in the adventitia, induces the Jak-STAT3 pathway during early A-II-induced atherosclerosis.

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“…1 Vascular remodeling during disease or injury involves altered expression of extracellular matrix proteins and cell surface integrins. [2][3][4] After arterial injury, laminin expression is reduced and fibronectin accumulates around VSMCs.…”

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confidence: 99%

Loss of the α7 Integrin Promotes Extracellular Signal-Regulated Kinase Activation and Altered Vascular Remodeling

Welser

Lange

Singer

et al. 2007

Circulation Research

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Abstract-VascularV ascular smooth muscle cell (VSMC) proliferation and migration are major underlying factors in the development and progression of various forms of cardiovascular disease, including atherosclerosis, postangioplasty restenosis, transplant arteriopathy, and pulmonary hypertension. 1 Vascular remodeling during disease or injury involves altered expression of extracellular matrix proteins and cell surface integrins. 2-4 After arterial injury, laminin expression is reduced and fibronectin accumulates around VSMCs. 5,6 These changes coincide with a phenotypic switch in which contractile VSMCs adopt a proliferative phenotype, possibly as part of a developmental program associated with wound repair. 2,4 Integrins are transmembrane mechanosensors that relay signals from the extracellular matrix to the cell cytoskeleton and/or cell signaling pathways to modulate cell shape, adhesion, differentiation, proliferation, and contraction. 7 Various integrins modulate cell proliferation, usually by crosstalk with proliferative cell signaling pathways or in cooperation with growth factor receptors. 8 The ␣7␤1 integrin is a major laminin-binding receptor in VSMCs, and expression of this integrin increases after differentiation. 9 Previous studies using blocking antibodies and peptides have demonstrated that the ␣7␤1 integrin mediates adhesion of VSMCs to laminin in vitro. 9,10 Expression of this integrin has also been shown to be modulated by chemically induced injury and platelet-derived growth factor in cultured rat VSMCs. 10,11 We have previously demonstrated that embryonic loss of the ␣7 integrin results in vascular defects and partial embryonic lethality, whereas in adult mice, loss of the ␣7 integrin results in VSMC hyperplasia. 12 Loss of the ␣7␤1 integrin in VSMCs leads to altered expression of other integrin chains, which may contribute to the vascular phenotype observed in ␣7 integrin-null mice. 12 These observations have led to the hypothesis that the ␣7␤1 integrin promotes the contractile phenotype of VSMCs, but the mechanism of this regulation is unclear.Activation of the extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase signaling Original

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Control of smooth muscle cell proliferation in vascular disease

Cited by 74 publications

References 61 publications

Platonin inhibited PDGF-BB-induced proliferation of rat vascular smooth muscle cells via JNK1/2-dependent signaling

Platonin inhibited PDGF-BB-induced proliferation of rat vascular smooth muscle cells via JNK1/2-dependent signaling

Angiotensin II induces IL-6 expression and the Jak-STAT3 pathway in aortic adventitia of LDL receptor-deficient mice

Loss of the α7 Integrin Promotes Extracellular Signal-Regulated Kinase Activation and Altered Vascular Remodeling

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