CRP is a novel ligand for the oxidized LDL receptor LOX-1

Shih, Heather H.; Zhang, Songwen; Cao, Wei; Hahn, Ashleigh; Wang, Juan; Paulsen, Janet; Harnish, Douglas C.

doi:10.1152/ajpheart.00938.2008

Cited by 67 publications

(55 citation statements)

References 30 publications

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“…Our data demonstrated that CRP enhanced the release of sLOX-1 from activated macrophages in vitro and increased circulating sLOX-1 levels in vivo, which agreed with previous studies showing sLOX-1 levels correlated signifi cantly with CRP levels in ACS patients ( 26 ). Recent studies have shown that CRP may act a ligand for LOX-1 and that the interaction of CRP with LOX-1 enhances endothelial infl ammation ( 27,28 ). Thus, when the CRP concentration reaches a high level, it may stimulate secretion of infl ammatory factors and directly impair endothelial function.…”

Section: Crp Regulated Slox-1 Release From Macrophages Derived From Psupporting

confidence: 92%

CRP enhances soluble LOX-1 release from macrophages by activating TNF-α converting enzyme

Zhao

Zhang

Wang

et al. 2011

Journal of Lipid Research

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An abundant increase in infl ammatory factors leads to acute infl ammatory diseases, such as acute coronary syndrome (ACS) ( 1 ). C-reactive protein (CRP), the prototypic marker of infl ammation, is one of the strongest predictors of cardiovascular events ( 2 ). Recent studies have demonstrated that CRP is present in atherosclerotic plaques and plays a pivotal role in promoting atherogenesis by regulating the expression and release of infl ammatory cytokines ( 3-5 ).Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1), a type II membrane glycoprotein acting as a receptor for oxidized low-density lipoprotein, mediates vascular dysfunction ( 3 ). LOX-1 is expressed on the cell surface and can be proteolytically cleaved at its extracellular domain and released as a soluble form (sLOX-1) ( 6 ). sLOX-1 level refl ects increased oxidative stress of vascular walls and has been identifi ed as a novel marker for early diagnosis of ACS ( 7,8 ). However, the exact mechanisms of sLOX-1 release from the cell membrane are poorly understood.Tumor necrosis factor-a converting enzyme (TACE), a disintegrin and metalloproteinase, mediates the release of growth factors, receptors, and adhesion molecules ( 9 ). TACE is synthesized in a latent form and activated by reactive oxygen species (ROS) before reaching the cell membrane ( 10, 11 ). Studies report that CRP can upregulate ROS production by activating NAPDH Abstract Circulating levels of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) play an important role in the development and progression of atherosclerosis. We hypothesized that the infl ammatory marker C-reactive protein (CRP) might stimulate sLOX-1 release by activating tumor necrosis factor-␣ converting enzyme (TACE). Macrophages differentiated from THP-1 cells were stimulated with TNF-␣ and further treated with CRP in the absence or presence of specifi c inhibitors or small interfering RNA (siRNA). Our results showed that CRP increased sLOX-1 release from activated macrophages in a dosedependent manner and that these effects were regulated by China (No. 60831003), and the National Natural Science Foundation of China (Nos. 30700301, 30971096, 30972809, and 81000126 Abbreviations: ACS, acute coronary syndrome; Apo, apocynin; CRP, C-reactive protein; DCF-DA, 2 ′ ,7 ′ -dichlorodihydrofl uorescein diacetate; Fc g R, Fc gamma receptor; IL, interleukin; LOX-1, lectin-like oxidized low-density lipoprotein receptor-1; NAC, N-acetylcysteine; PBMC, peripheral blood mononuclear cell; PMSF, phenylmethyl sulfonylfl uoride; ROS, reactive oxygen species; siRNA, small interfering RNA; TACE, tumor necrosis factor-a converting enzyme; TAPI-1, tumor necrosis factor-a protease inhibitor 1; TNF-a , tumor necrosis factor-a . 1 X. Q. Zhao and M. W. Zhang contributed equally to this work.

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Section: Crp Regulated Slox-1 Release From Macrophages Derived From Psupporting

confidence: 92%

CRP enhances soluble LOX-1 release from macrophages by activating TNF-α converting enzyme

Zhao

Zhang

Wang

et al. 2011

Journal of Lipid Research

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“…In this study, we established a new rapid and sensitive AlphaScreen SureFire assay as a strategy for studying the pharmacology of GPR55. This method has been used to explore ligands of the cytokine receptors (30), LDL endothelial receptor (31), and potassium channel TREK-1 receptors (32) and to develop antagonists for other intracellular targets (33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

Modulation of l-α-Lysophosphatidylinositol/GPR55 Mitogen-activated Protein Kinase (MAPK) Signaling by Cannabinoids

Anavi‐Goffer

Baillie

Irving

et al. 2012

Journal of Biological Chemistry

139

132

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Background:The endogenous L-␣-lysophosphatidylinositol activates GPR55. Results: Structural analogues of SR141716A act both as agonists alone and as inhibitors of L-␣-lysophosphatidylinositol. Certain CB 2 receptor agonists also modulate GPR55 activity. Conclusion: Certain cannabinoids can both activate GPR55 and attenuate L-␣-lysophosphatidylinositol-mediated phosphorylated ERK1/2 activation. This has mechanistic implications for the antinociceptive effects of certain CB 2 agonists. Significance: Cannabinoid ligands have complex interactions with the L-␣-lysophosphatidylinositol/GPR55 signaling system.

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“…However, we did not find any significant differences in the expression on CD32 and CD64 in pulmonary vascular tissue from CTEPH and nonthromboembolic PH patients. It has recently been shown that CRP is also a ligand of LOX-1, the primary endothelial receptor for oxLDL [36]. Moreover, oxLDL induced ICAM-1 and VCAM-1 mRNA expression [36] and ET-1 secretion by human umbilical vein ECs [37].…”

Section: In Vitro Effects Of Crp On Pulmonary Vascular Cellsmentioning

confidence: 99%

Effects of C-reactive protein on human pulmonary vascular cells in chronic thromboembolic pulmonary hypertension

et al. 2012

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Chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by proximal pulmonary vascular obstruction by thrombo-fibrotic material, the origin of which has not been elucidated. Enhanced inflammation could contribute to persistent obstruction by impairing pulmonary vascular cell function in CTEPH. We investigated C-reactive protein (CRP) effects on pulmonary vascular cell function in vitro.Primary cultures of proximal pulmonary endothelial cells (ECs) and smooth muscle cells (SMCs) from CTEPH and nonthromboembolic pulmonary hypertension (PH) patients were established. Recombinant CRP effects on mitogenic activity, adhesion capacity, endothelin-1 and von Willebrand factor (vWF) secretion and intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule-1 expression were investigated in ECs and/or SMCs. Expression of the CRP receptor, lectin-like oxidised low-density lipoprotein receptor (LOX)-1, was evaluated in proximal pulmonary arterial tissue and cells by Western blotting and immunofluorescence.CRP increased CTEPH-SMC proliferation by 250%. CRP increased adhesion capacity, endothelin-1 and vWF secretion by CTEPH-ECs by 37%, 129% and 694%, respectively. CRP-induced adhesion of CTEPH-ECs to monocytes was mediated by ICAM-1. CRP had no effect on cells from nonthromboembolic PH patients, probably because of overexpression of LOX-1 in CTEPH. Local expression of CRP was detected in ECs and SMCs within pulmonary arterial tissue.CRP may contribute to persistent obstruction of proximal pulmonary arteries in CTEPH by promoting vascular remodelling, endothelial dysfunction and in situ thrombosis. KEYWORDS: C-reactive protein, chronic thromboembolic pulmonary hypertension, endothelial cells, inflammation, smooth muscle cells C hronic thromboembolic pulmonary hypertension (CTEPH) is one of the main causes of severe pulmonary hypertension. CTEPH is characterised by intraluminal thrombus organisation and fibrous stenosis or complete obliteration of proximal pulmonary arteries. The consequence is an increased pulmonary vascular resistance resulting in pulmonary hypertension (PH) and progressive right heart failure. Pulmonary embolism, either as single or recurrent episodes, is thought to be the initiating event followed by progressive pulmonary vascular remodelling. CTEPH mainly differs from pulmonary arterial hypertension (PAH) by the proximal location of pulmonary artery obliteration [1].To date, the physiopathology of CTEPH remains poorly understood. Proximal lesions share similarities with atherosclerotic plaques, including media thickening and neointima formation [2]. Besides evidence of dysregulated thrombosis and/or thrombolysis, an elevated prevalence of inflammatory diseases has been observed in CTEPH patients [3]. Accordingly, plasma levels of tumour necrosis factor-a are elevated in CTEPH [4] and elevated pulmonary vascular resistance is correlated with increased expression of the CCL2 chemokine monocyte chemoattractant protein-1 in the plasma and large pulmonary arteries of CTE...

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CRP is a novel ligand for the oxidized LDL receptor LOX-1

Cited by 67 publications

References 30 publications

CRP enhances soluble LOX-1 release from macrophages by activating TNF-α converting enzyme

CRP enhances soluble LOX-1 release from macrophages by activating TNF-α converting enzyme

Modulation of l-α-Lysophosphatidylinositol/GPR55 Mitogen-activated Protein Kinase (MAPK) Signaling by Cannabinoids

Effects of C-reactive protein on human pulmonary vascular cells in chronic thromboembolic pulmonary hypertension

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