Adhesion Molecule Expression in Fibroblasts

Chen, Kui; Chen, Jiawei; Liu, Yong; Xie, Jingyuan; Li, Dayuan; Sawamura, Tatsuya; Hermonat, Paul L.; Mehta, Jawahar L.

doi:10.1161/01.hyp.0000179045.95915.b0

Cited by 32 publications

(14 citation statements)

References 42 publications

(41 reference statements)

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“…[30][31][32][33][34] Our study indicates that paeonol prevents monocytes adhesion to vascular endothelial cells induced by ox-LDL in dosedependent manner. Paeonol, directly or indirectly, also alters the expression of adhesion molecules and reduces leukocytes infiltration into vascular endothelium.…”

Section: Discussionmentioning

confidence: 52%

Paeonol Inhibits Oxidized Low Density Lipoprotein-Induced Monocyte Adhesion to Vascular Endothelial Cells by Inhibiting the Mitogen Activated Protein Kinase Pathway

Wang

Dai

Zhong

et al. 2012

Biological & Pharmaceutical Bulletin

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Atherosclerosis is a chronic inflammatory disease characterized by increased expression of adhesion molecules, which contribute to monocytes adhesion to vascular endothelial cells (VECs). Paeonol, an active compound isolated from cortex Moutan, has been shown to have therapeutic effects on atherosclerotic animals. The present study aims to investigate whether paeonol can inhibit monocyte adhesion to vascular endothelial cells induced by oxidized Low-Density Lipoprotein (ox-LDL) and its possible therapeutic molecular mechanism. Exposure to ox-LDL (50, 100 µg/mL) induced damaged to VECs leading to decreased survival rates (p<0.01). Paeonol (7.2-18.0 µM) partially restored survival and reduced lactate dehydrogenase (LDH) release in VECs in a concentration-dependent manner (p<0.01). Adhesion of monocytes to VECs was dramatically prevented by paeonol at 21.6 and 25.2 μM (p<0.01). In addition, paeonol (14.4-21.6 μM) repressed the expression of vascular cell adhesion molecule-1 (VCAM-1) and lowered the levels of phosphor-c-Jun N-terminal kinase (P-JNK)1/2, phosphor-extracellular signal-regulated kinase (P-ERK)1/2 and P-p38 in a dose-dependent manner. The molecular effects of paeonol were more pronouced when companied with mitogen activated protein kinases (MAPKs) inhibitors. These data suggest that paeonol (10.8-25.2 μM), at certain concentrations, prevents monocyte adhesion to VEC induced by ox-LDL, probably by means of blocking one or more target proteins on MAPKs signaling pathway. These results indicate that paeonol has potential protective effects on the development of atherosclerosis.

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Section: Discussionmentioning

confidence: 52%

Paeonol Inhibits Oxidized Low Density Lipoprotein-Induced Monocyte Adhesion to Vascular Endothelial Cells by Inhibiting the Mitogen Activated Protein Kinase Pathway

Wang

Dai

Zhong

et al. 2012

Biological & Pharmaceutical Bulletin

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“…In keeping with previous studies in rodent cardiac fibroblasts, 5,17 Ang II exposure induced procollagen I expression, but the procollagen I expression was decreased by LOX deletion. Chen et al 6 showed that the overexpression of LOX-1 in rat cardiac fibroblasts enhances the expression of collagen I and the phosphorylation of p38 MAPK. These observations further suggest that the Ang II (AT1R)-ROS-LOX-1 loop might directly regulate the development of cardiac remodeling in mice with an Ang II-induced increase in blood pressure.…”

Section: Discussionmentioning

confidence: 99%

“…5,6,11 To mimic the in vivo state, we treated mouse cardiac fibroblasts with Ang II (1 mol/L) for 24 hours. Prolonged exposure of cardiac fibroblasts from wild-type mice to Ang II induced dichlorofluorescein fluorescence and NADPH oxidase (p47 phox and p22 phox subunits) expression, but these changes were much less pronounced in fibroblasts from LOX-1 KO mice despite their treatment with Ang II (PϽ0.01).…”

Section: Studies In Cultured Cardiac Fibroblastsmentioning

confidence: 99%

“…4 In addition, activation of both AT1R and LOX-1 enhances the growth of cardiac fibroblasts and promotes collagen synthesis. 5,6 Although LOX-1 mRNA expression is minimal in normal arterial tissues, it is markedly upregulated in vascular tissues of spontaneously hypertensive animals, suggesting a correlation between LOX-1 and hypertension. 7 This concept is supported by in vitro observations that Ang II upregulates LOX-1 expression, 2 and angiotensin-converting enzyme inhibitors and AT1R blockers decrease LOX-1 expression.…”

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confidence: 99%

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Modulation of Angiotensin II–Mediated Hypertension and Cardiac Remodeling by Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Deletion

Dandapat

Sun

et al. 2008

Hypertension

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Abstract-Angiotensin II via type 1 receptor activation upregulates the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), and LOX-1 activation, in turn, upregulates angiotensin II type 1 receptor expression. We postulated that interruption of this positive feedback loop might attenuate the genesis of angiotensin II-induced hypertension and subsequent cardiac remodeling. To examine this postulate, LOX-1 knockout and wild-type mice were infused with angiotensin II or norepinephrine (control for angiotensin II) for 4 weeks. Angiotensin II-, but not norepinephrine-, induced hypertension was attenuated in LOX-1 knockout mice. Angiotensin II-induced cardiac remodeling was also attenuated in LOX-1 knockout mice. Importantly, angiotensin II type 1 receptor expression was reduced, and the expression and activity of endothelial NO synthase were preserved in the tissues of LOX-1 knockout mice given angiotensin II. Reactive oxygen species generation, nicotinamide-adenine dinucleotide phosphate oxidase expression, and phosphorylation of p38 and p44/42 mitogen-activated protein kinases were also much less pronounced in the LOX-1 knockout mice given angiotensin II. These alterations in biochemical and structural abnormalities were associated with preservation of cardiac hemodynamics in the LOX-1 knockout mice. To confirm that fibroblast function is modulated in the absence of LOX-1, cardiac fibroblasts from wild-type and LOX-1 knockout mice were treated with angiotensin II. Indeed, LOX-1 knockout mice cardiac fibroblasts revealed an attenuated profibrotic response on treatment with angiotensin II. These observations provide strong evidence that LOX-1 is a key modulator of the development of angiotensin II-induced hypertension and subsequent cardiac remodeling. (Hypertension. 2008;52:556-562.)Key Words: angiotensin Ⅲ hypertension Ⅲ cardiac remodeling Ⅲ LOX-1 Ⅲ oxidative stress C ardiac remodeling is initially an adaptive response to several forms of cardiac stress states, such as hypertension. Sustained remodeling results in heart failure and is a powerful independent risk factor for cardiac morbidity and mortality. 1 Therefore, identification of the molecular mechanisms involved in cardiac remodeling is an important challenge for the cardiovascular biologists.The renin-angiotensin system and its effector hormone, angiotensin II (Ang II), have well-known endocrine properties that contribute to cardiac remodeling and heart failure. Previous studies have shown that Ang II via type 1 receptor (AT1R) activation stimulates the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). 2 In turn, activation of LOX-1 upregulates AT1R expression. 3 Activation of both AT1R and LOX-1 induces a state of oxidative stress. 4 In addition, activation of both AT1R and LOX-1 enhances the growth of cardiac fibroblasts and promotes collagen synthesis. 5,6 Although LOX-1 mRNA expression is minimal in normal arterial tissues, it is markedly upregulated in vascular tissues of spontaneously hypertensive...

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“…It is also up-regulated in response to oxidative stress (7). Activation of LOX-1 enhances the growth of cardiac fibroblasts and promotes collagen synthesis (8,9). It has been reported that TGF␤ 1 can regulate LOX-1 expression in vascular endothelial cells, smooth muscle cells, and monocytes/macrophages (10,11).…”

mentioning

confidence: 99%

Regulation of TGFβ1-mediated Collagen Formation by LOX-1

Dandapat

Sun

et al. 2008

Journal of Biological Chemistry

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Transforming growth factor ␤ 1 (TGF␤ 1 ) activation leads to tissue fibrosis. Here, we report on the role of LOX-1, a lectin-like 52-kDa receptor for oxidized low density lipoprotein, in TGF␤ 1 -mediated collagen expression and underlying signaling in mouse cardiac fibroblasts. TGF␤ 1 was overexpressed in wildtype (WT) and LOX-1 knock-out mouse cardiac fibroblasts by transfection with adeno-associated virus type 2 vector carrying the active TGF␤ 1 moiety (AAV/TGF␤ 1 ACT ). Transfection of WT mouse cardiac fibroblasts with AAV/TGF␤ 1 ACT markedly enhanced the expression of NADPH oxidases (p22 phox , p47 phox , and gp91 phox subunits) and LOX-1, formation of reactive oxygen species, and collagen synthesis, concomitant with an increase in the activation of p38 and p44/42 mitogen-activated protein kinases (MAPK). The TGF␤ 1 -mediated increase in collagen synthesis was markedly attenuated in the LOX-1 knock-out mouse cardiac fibroblasts as well as in WT mouse cardiac fibroblasts treated with a specific anti-LOX-1 antibody. Treatment with anti-LOX-1 antibody also reduced NADPH oxidase expression and MAPK activation. The NADPH oxidase inhibitors and gp91phox small interfering RNA reduced LOX-1 expression, MAPK activation, and collagen formation. The p38 MAPK inhibitors as well as the p44/42 MAPK inhibitors reduced collagen formation without affecting LOX-1 expression in cardiac fibroblasts. These observations suggest that collagen synthesis in cardiac fibroblasts involves a facilitative interaction between TGF␤ 1 -NADPH oxidase and LOX-1. Further, the activation of MAPK pathway appears to be downstream of TGF␤ 1 -reactive oxygen species-LOX-1 cascade.Cardiac fibrosis, characterized by accumulation of matrix proteins in the extracellular space in the perivascular region, is closely associated with the development of heart failure. Among the extracellular matrix proteins, up to 85% are collagens, of which type 1 (collagen I) and type 3 (collagen III) constitute two-thirds of total collagens in most tissues (1). Transforming growth factor (TGF) 3 ␤ 1 is one of the most pleiotropic and multifunctional peptides known (2). It exerts potent effects on many different cell types and is involved in a wide variety of biological processes (2). The cellular actions of TGF␤ 1 are dependent not only on the cell type but also on its state of differentiation and the cytokine milieu (3). Although there is evidence that TGF␤ 1 stimulates fibroblast growth, enhances collagen synthesis, and suppresses collagen degradation (2) ACT that appears to be functionally relevant in the process of ischemia-reperfusion (5).LOX-1 is a lectin-like receptor for oxidized low density lipoprotein (6). It is also up-regulated in response to oxidative stress (7). Activation of LOX-1 enhances the growth of cardiac fibroblasts and promotes collagen synthesis (8, 9). It has been reported that TGF␤ 1 can regulate LOX-1 expression in vascular endothelial cells, smooth muscle cells, and monocytes/macrophages (10, 11). Another study showed that LOX-1 blockade reduc...

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Adhesion Molecule Expression in Fibroblasts

Cited by 32 publications

References 42 publications

Paeonol Inhibits Oxidized Low Density Lipoprotein-Induced Monocyte Adhesion to Vascular Endothelial Cells by Inhibiting the Mitogen Activated Protein Kinase Pathway

Paeonol Inhibits Oxidized Low Density Lipoprotein-Induced Monocyte Adhesion to Vascular Endothelial Cells by Inhibiting the Mitogen Activated Protein Kinase Pathway

Modulation of Angiotensin II–Mediated Hypertension and Cardiac Remodeling by Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Deletion

Regulation of TGFβ1-mediated Collagen Formation by LOX-1

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