Augmentation of Proliferation of Vascular Smooth Muscle Cells by Plasminogen Activator Inhibitor Type 1

Chen, Yabing; Budd, Ralph C.; Kelm, Robert J.; Sobel, Burton E.; Schneider, David J.

doi:10.1161/01.atv.0000227514.50065.2a

Cited by 76 publications

(67 citation statements)

References 51 publications

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“…ERK signaling promotes VSMC growth while inhibition of NF-jB decreases the proliferation of VSMCs (Maruyama et al 1997). In addition, increased expression of PAI-1 inhibits apoptosis and promotes cell proliferation in VSMCs through downstream mediators (Chen et al 2006). Our results clearly show that knockdown of RAGE inhibits ERK phosphorylation, NF-jB translocation to the nucleus, and consequent cytokine expression in HUVECs, as well as secretory MMP-2 and -9 activity and VSMC proliferation in our co-culture system.…”

Section: Discussionsupporting

confidence: 57%

Glycolaldehyde-derived advanced glycation end products (glycol-AGEs)-induced vascular smooth muscle cell dysfunction is regulated by the AGES-receptor (RAGE) axis in endothelium

Nam

Son

Lee

et al. 2015

Cell Communication & Adhesion

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Advanced glycation end-products (AGEs) are involved in the development of vascular smooth muscle cell (VSMC) dysfunction and the progression of atherosclerosis. However, AGEs may indirectly affect VSMCs via AGEs-induced signal transduction between monocytes and human umbilical endothelial cells (HUVECs), rather than having a direct influence. This study was designed to elucidate the signaling pathway underlying AGEs-RAGE axis influence on VSMC dysfunction using a co-culture system with monocytes, HUVECs and VSMCs. AGEs stimulated production of reactive oxygen species and pro-inflammatory mediators such as tumor necrosis factor-a and interleukin1b via extracellular-signal-regulated kinases phosphorylation and nuclear factor-jB activation in HUVECs. It was observed that AGEs-induced pro-inflammatory cytokines increase VSMC proliferation, inflammation and vascular remodeling in the co-culture system. This result implies that RAGE plays a role in AGEs-induced VSMC dysfunction. We suggest that the regulation of signal transduction via the AGEs-RAGE axis in the endothelium can be a therapeutic target for preventing atherosclerosis.ARTICLE HISTORY

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Section: Discussionsupporting

confidence: 57%

Glycolaldehyde-derived advanced glycation end products (glycol-AGEs)-induced vascular smooth muscle cell dysfunction is regulated by the AGES-receptor (RAGE) axis in endothelium

Nam

Son

Lee

et al. 2015

Cell Communication & Adhesion

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“…Increased levels of PAI-1 have also been detected in vascular lesions induced by atherosclerosis or balloon catheter injury (11,46). PAI-1 promotes proliferation and protects arterial smooth muscle cells from apoptosis, thus there is an increased likelihood of hyperplasia following angioplasty when PAI-1 expression is abnormally elevated (9). Our findings extend these conclusions to cerebral arteries, supporting a role for OPN and PAI-1 in the proliferative changes observed in cerebral arteries of hypertensive rats.…”

Section: Discussionsupporting

confidence: 79%

Genes overexpressed in cerebral arteries following salt-induced hypertensive disease are regulated by angiotensin II, JunB, and CREB

Rose¹,

Bond²,

Tighe³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Rose P, Bond J, Tighe S, Toth MJ, Wellman TL, de Montiano EM, Lewinter MM, Lounsbury KM. Genes overexpressed in cerebral arteries following salt-induced hypertensive disease are regulated by angiotensin II, JunB, and CREB. Am J Physiol Heart Circ Physiol 294: H1075-H1085, 2008. First published December 21, 2007 doi:10.1152/ajpheart.00913.2007.-Although changes in gene expression are necessary for arterial remodeling during hypertension, the genes altered and their mechanisms of regulation remain uncertain. The goal of this study was to identify cerebral artery genes altered by hypertension and define signaling pathways important in their regulation. Intact cerebral arteries from Dahl salt-sensitive normotensive and hypertensive high-salt (HS) rats were examined by immunostaining, revealing an increased phosphorylation of extracellular signalregulated kinase 1/2 (ERK1/2) and expression of the proliferative marker Ki-67 in arteries from hypertensive animals. Arterial RNA analyzed by microarray and validated with RT-quantitative PCR revealed that jun family member junB and matricellular genes plasminogen activator inhibitor-1 (PAI-1) and osteopontin (OPN) were significantly overexpressed in HS arteries. Fisher exact test and annotation-based gene subsets showed that genes upregulated by Jun and Ca 2ϩ /cAMP-response element-binding protein (CREB) were overrepresented. A model of cultured rat cerebrovascular smooth muscle cells was used to test the hypothesis that angiotensin II (ANG II), JunB, and CREB are important in the regulation of genes identified in the rat hypertension model. ANG II induced a transient induction of junB and a delayed induction of PAI-1 and OPN mRNA levels, which were reduced by ERK inhibition with U-0126. Silencing junB using small-interfering RNA reduced mRNA levels of OPN but not PAI-1. The silencing of CREB reduced PAI-1 induction by ANG II but enhanced the transcription of OPN. Together, these results suggest that salt-induced hypertensive disease promotes changes in matricellular genes that are stimulated by ANG II, regulated by ERK, and selectively regulated by JunB and CREB. microarray; Dahl rat; brain arteries; mitogen-activated protein kinase signaling; transcription factors HYPERTENSION IS A multifactorial disease, linked to both genetic and environmental origins, that ultimately causes direct alterations on the vasculature including smooth muscle cell proliferation and vascular remodeling (2, 34, 48). Rats selectively bred for hypertension studies have been useful models to study the complexity of human essential hypertension (42). The Dahl salt-sensitive (Dahl S) genetic model of hypertension is a paradigm of low renin hypertension observed in humans. Two genetic defects have been identified in the Dahl S strain including a mutation of the ␣ 1 Na ϩ , K ϩ -ATPase gene, affecting the renal basolateral epithelia throughout the nephron, and a restriction fragment-length polymorphism in the renin gene, affecting the proximal tubule (19,44).In response to the Na ϩ challenge of a high-...

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“…29 In agreement with these findings, VSMCs explanted from SM22-PAI-knockin mice exhibited a 2-fold greater expression of PAI-1 and an attenuated migration pattern. 36 Moreover, flow-induced SMC migration was attenuated when PAI-1 Ϫ/Ϫ SMCs were cultured in the presence of ECs. 29 Thus, PAI-1 expression in VSMCs plays a role in limiting flow-induced VSMC migration.…”

Section: Discussionmentioning

confidence: 99%

C5a Receptor Targeting in Neointima Formation After Arterial Injury in Atherosclerosis-Prone Mice

et al. 2010

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Background-Receptor binding of complement C5a leads to proinflammatory activation of many cell types, but the role of receptor-mediated action during arterial remodeling after injury has not been studied. In the present study, we examined the contribution of the C5a receptor (C5aR) to neointima formation in apolipoprotein E-deficient mice employing a C5aR antagonist (C5aRA) and a C5aR-blocking monoclonal antibody. Methods and Results-Mice fed an atherogenic diet were subjected to wire-induced endothelial denudation of the carotid artery and treated with C5aRA and anti-C5aR-blocking monoclonal antibody or vehicle control. Compared with controls, neointima formation was significantly reduced in mice receiving C5aRA or anti-C5aR-blocking monoclonal antibody for 1 week but not for 3 weeks, attributable to an increased content of vascular smooth muscle cells, whereas a marked decrease in monocyte and neutrophil content was associated with reduced vascular cell adhesion molecule-1. As assessed by immunohistochemistry, reverse transcription polymerase chain reaction, and flow cytometry, C5aR was expressed in lesional and cultured vascular smooth muscle cells, upregulated by injury or tumor necrosis factor-␣, and reduced by C5aRA. Plasma levels and neointimal plasminogen activator inhibitor-1 peaked 1 week after injury and were downregulated in C5aRA-treated mice. In vitro, C5a induced plasminogen activator inhibitor-1 expression in endothelial cells and vascular smooth muscle cells in a C5aRA-dependent manner, possibly accounting for higher vascular smooth muscle cell immigration. Conclusions-One-week treatment with C5aRA or anti-C5aR-blocking monoclonal antibody limited neointimal hyperplasia and inflammatory cell content and was associated with reduced vascular cell adhesion molecule-1 expression. 3 and adverse cardiovascular events have been correlated with C5a plasma levels. 4 C5a is a potent soluble anaphylotoxic and chemotactic inflammatory mediator promoting the recruitment and activation of neutrophils and monocytes. 5 C5a specifically binds to its receptor C5aR (also named CD88), a rhodopsin-type receptor expressed in various cell types. In addition to immune cells (neutrophils, eosinophils, basophils, monocytes/macrophages, mast cells, dendritic cells, and T cells), C5aR has also been detected in nonimmune cells, including neuronal and endothelial cells (ECs), and in different tissues (lung, kidney, liver, spleen, intestine, skin, and heart). 6 Binding of C5a to C5aR leads to cellular activation, including adhesion and chemotaxis. 7 Enhanced surface and messenger RNA (mRNA) expression of C5aR was found in microvascular ECs after exposure to lipopolysaccharide, interferon-␥, and interleukin-6, concomitant with an upregulation of macrophage-inflammatory protein-2/ CXCL2 and macrophage chemoattractant protein-1/CCL2. 8 Stimulation of ECs with C5a increases the gene expression of adhesion molecules, 9,10 cytokines, chemokines, and related receptors. 9,11 Clinical Perspective on p 1036In C5aR-deficient mice, IgG...

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Augmentation of Proliferation of Vascular Smooth Muscle Cells by Plasminogen Activator Inhibitor Type 1

Cited by 76 publications

References 51 publications

Glycolaldehyde-derived advanced glycation end products (glycol-AGEs)-induced vascular smooth muscle cell dysfunction is regulated by the AGES-receptor (RAGE) axis in endothelium

Glycolaldehyde-derived advanced glycation end products (glycol-AGEs)-induced vascular smooth muscle cell dysfunction is regulated by the AGES-receptor (RAGE) axis in endothelium

Genes overexpressed in cerebral arteries following salt-induced hypertensive disease are regulated by angiotensin II, JunB, and CREB

C5a Receptor Targeting in Neointima Formation After Arterial Injury in Atherosclerosis-Prone Mice

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