Inducible Expression of Lectin-like Oxidized LDL Receptor-1 in Vascular Endothelial Cells

Kume, Noriaki; Murase, Takatoshi; Moriwaki, Hisataka; Aoyama, Takuma; Sawamura, Tatsuya; Masaki, Τοmoh; Kita, Toru

doi:10.1161/01.res.83.3.322

Cited by 288 publications

(198 citation statements)

References 36 publications

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“…Kume et al (1998) showed that TNF-α increases LOX-1 expression in a concentration-dependent manner in bovine aortic endothelial cells. The time-course experiments showed that LOX-1 mRNA levels peaked at 2 hours and remained elevated for at least 21 hours.…”

Section: Enhancement Of Lox-1 Expression By Atherosclerosis-related Rmentioning

confidence: 99%

Lectin‐like Oxidized Low‐density Lipoprotein Receptor‐1, a New Promising Target for the Therapy of Atherosclerosis?

Chen

Zhang

2007

Cardiovascular Drug Reviews

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Endothelial activation and dysfunction induced by oxidized modified low-density lipoprotein (ox-LDL) is one of the key steps in the initiation of atherosclerosis. Recent studies have shown that a new lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) mediates the recognition and internalization of ox-LDL. LOX-1 is the main receptor for ox-LDL and may play an important role in the pathogenesis of hypertension, diabetes, and, especially, of atherosclerosis. The potential role of LOX-1 in the pathogenesis of atherosclerosis includes: endocytosis of ox-LDL, expression co-location with atherosclerosis enhanced by atherosclerosis-related risk factors, elevated LOX-1 protein in cardiovascular disease, effects related to atherosclerosis and eliminated by antiatherosclerotic drugs. Identification and regulation of LOX-1 and understanding its signal transduction pathways might improve our insight toward the pathogenesis of atherosclerosis and provide a selective treatment approach. LOX-1 might be a potential and promising target for the development of novel antiatherosclerotic drugs. However, due to limited knowledge about LOX-1, there are still many questions to be answered.

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Section: Enhancement Of Lox-1 Expression By Atherosclerosis-related Rmentioning

confidence: 99%

Lectin‐like Oxidized Low‐density Lipoprotein Receptor‐1, a New Promising Target for the Therapy of Atherosclerosis?

Chen

Zhang

2007

Cardiovascular Drug Reviews

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“…21 Studies on the regulation of LOX-1 expression in EC, M⌽, and SMC revealed upregulation of LOX-1 expression after incubation with PMA, 16,17,19 an activator of PKC. Our study also showed a 3-fold upregulation of LOX-1 mRNA and protein expression after incubation with PMA, comparable with the detected upregulation of LOX-1 expression after incubation with IL-1␣, IL-1␤, and TNF.…”

Section: Lox-1 Expression Is Upregulated By Proinflammatory Cytokinesmentioning

confidence: 99%

“…15 Atherosclerotic lesions containing lipid-laden foam cells are the hallmark of the inflammatory state, and recent investigations showed that inflammatory stimuli modulate LOX-1 expression in vitro. IL-4 induces LOX-1 expression in M⌽ 16 and tumor necrosis factor (TNF)-␣ and transforming growth factor (TGF)-␤ upregulate LOX-1 expression in EC, 17,18 M⌽, 18 -20 and SMC. 18,19 Activation of protein kinase C (PKC), which plays a central role in mediating inflammatory responses, 21 upregulates LOX-1 expression in EC, 17 M⌽, 16,19 and SMC.…”

mentioning

confidence: 99%

“…IL-4 induces LOX-1 expression in M⌽ 16 and tumor necrosis factor (TNF)-␣ and transforming growth factor (TGF)-␤ upregulate LOX-1 expression in EC, 17,18 M⌽, 18 -20 and SMC. 18,19 Activation of protein kinase C (PKC), which plays a central role in mediating inflammatory responses, 21 upregulates LOX-1 expression in EC, 17 M⌽, 16,19 and SMC. 19 Further, it is known that peroxisome proliferator-activated receptors (PPARs), which influence the transcriptional regulation of a large number of genes affecting inflammation, 22 modulate LOX-1 expression in vitro: PPAR␣ activators increase LOX-1 expression in EC, 23 and PPAR␥ activators inhibit TNF-␣ induced LOX-1 expression in EC.…”

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confidence: 99%

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Proinflammatory Cytokines Regulate LOX-1 Expression in Vascular Smooth Muscle Cells

Hofnagel¹,

Luechtenborg²,

Stolle³

et al. 2004

ATVB

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Objective-Atherogenesis represents a type of chronic inflammation and involves elements of the immune response, eg, the expression of proinflammatory cytokines. In advanced atherosclerotic lesions, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is expressed in endothelial cells, macrophages, and smooth muscle cells (SMCs). In vitro, the expression of LOX-1 is induced by inflammatory cytokines like TNF-␣ and transforming growth factor (TGF)-␤. Therefore, LOX-1 is thought to be upregulated locally in response to cytokines in vivo. Methods and Results-We determined by reverse-transcription polymerase chain reaction (PCR) and Western blot analysis whether the mediators of the acute phase response in inflammation, IL-1␣, IL-1␤, and TNF-␣, regulate LOX-1 expression in cultured SMC, and whether this regulation is influenced by peroxisome proliferator-activated receptor ␥ (PPAR␥). We studied by immunohistochemistry whether these cytokines are spatially correlated with LOX-1 expression in advanced atherosclerotic lesions. We found upregulation of LOX-1 expression in SMC in a dose-and time-dependent manner after incubation with IL-1␣, IL-1␤, and TNF-␣. Simultaneous incubation with these cytokines at saturated concentrations had an additive effect on LOX-1 expression. The PPAR␥ activator, 15d-PGJ 2 , however, inhibited IL-1␤-induced upregulation of LOX-1. In the intima of atherosclerotic lesions regions of IL-1␣, IL-1␤, and TNF-␣ expression corresponded to regions of LOX-1 expression. Conclusion-We suppose that upregulated LOX-1 expression in SMC of advanced atherosclerotic lesions is a response to these proinflammatory cytokines. Moreover, the proinflammatory effects of these cytokines can be decreased by the antiinflammatory effect of PPAR␥.

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“…4 LOX-1 is a single transmembrane domain protein with its carboxyl-terminal end containing an extracytoplasmic C-type lectin domain, and is expressed in various cells, including endothelial cells, macrophages, vascular smooth muscle cells, and dendritic cells. 3,[5][6][7] Expression of LOX-1 is enhanced by oxidative stress, 8 stimulation by mediators of inflammation such as IL-1b 9,10 and tumor necrosis factor (TNF)-a, 11 its ligand ox-LDL, 12 and fluid shear stress. 13 In rat zymosan-induced arthritis, induction of the expression of LOX-1 was accompanied by accumulation of ox-LDL in chondrocytes, suggesting the possible interaction of ox-LDL and LOX-1 in cartilage.…”

Section: Introductionmentioning

confidence: 99%

Cyclic tensile stretch load and oxidized low density lipoprotein synergistically induce lectin‐like oxidized ldl receptor‐1 in cultured bovine chondrocytes, resulting in decreased cell viability and proteoglycan synthesis

Akagi

Nishimura

Yoshida

et al. 2006

Journal Orthopaedic Research

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Mechanical stimulation is known to be an essential factor in the regulation of cartilage metabolism. We tested the hypothesis that expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) can be modulated by cyclic tensile stretch load in chondrocytes. Cyclic loading of repeated stretch stress at 10 cycles per minute with 10 kPa of stress for 6 h induced expression of LOX-1 to 2.6 times control in cultured bovine articular chondrocytes, equivalent to the addition of 10 mg/mL oxidized low density lipoprotein (ox-LDL) (2.4 times control). Application of the cyclic load to the chondrocytes along with 10 mg/mL ox-LDL resulted in synergistically increased LOX-1 expression to 6.3 times control. Individual application of cyclic loading and 10 mg/mL ox-LDL significantly suppressed chondrocytes viability (84.6% AE 3.4% and 80.9% AE 3.2% of control at 24 h, respectively; n ¼ 3; p < 0.05) and proteoglycan synthesis [81.0% AE 7.1% and 85.7% AE 5.2% of control at 24 h, respectively; p < 0.05 when compared with 94.6% AE 4.6% for native-LDL (n ¼ 3)]. Cyclic loading and 10 mg/mL ox-LDL synergistically affected cell viability and proteoglycan synthesis, which were significantly suppressed to 45.6% AE 4.9% and 48.7% AE 6.7% of control at 24 h, respectively (n ¼ 3; p < 0.01 when compared with individual application of cyclic loading or 10 mg/ mL ox-LDL). In this study, we demonstrated synergistic effects of cyclic tensile stretch load and ox-LDL on cell viability and proteoglycan synthesis in chondrocytes, which may be mediated through enhanced expression of LOX-1 and which has important implications in the progression of cartilage degeneration in osteoarthritis. ß

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Inducible Expression of Lectin-like Oxidized LDL Receptor-1 in Vascular Endothelial Cells

Cited by 288 publications

References 36 publications

Lectin‐like Oxidized Low‐density Lipoprotein Receptor‐1, a New Promising Target for the Therapy of Atherosclerosis?

Lectin‐like Oxidized Low‐density Lipoprotein Receptor‐1, a New Promising Target for the Therapy of Atherosclerosis?

Proinflammatory Cytokines Regulate LOX-1 Expression in Vascular Smooth Muscle Cells

Cyclic tensile stretch load and oxidized low density lipoprotein synergistically induce lectin‐like oxidized ldl receptor‐1 in cultured bovine chondrocytes, resulting in decreased cell viability and proteoglycan synthesis

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