Comparative effect of lipoxygenase products of arachidonic acid on rat aortic smooth muscle cell migration

Nakao, Junko; Ooyama, Toshiro; Ito, Hideki; Chang, Wen Chang; Murota, Sei‐itsu

doi:10.1016/0021-9150(82)90008-9

Cited by 148 publications

(48 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7,[17][18][19] Furthermore, the 12-LO product 12(S)-HETE could induce VSMC migration and extracellular matrix production. 20,21 Ang II-induced hypertrophy as well as PDGF-induced chemotactic effects were significantly blocked by pharmacological LO inhibitors and a molecular inhibitor, 12-LO ribozyme. 17,[21][22][23] Expression of 12/15-LO was also increased in balloon-injured arteries, whereas 12-LO ribozymes and pharmacological inhibitors reduced the extent of neointimal thickening in these injured rat carotid arteries.…”

mentioning

confidence: 98%

Reduced Growth Factor Responses in Vascular Smooth Muscle Cells Derived from 12/15-Lipoxygenase–Deficient Mice

et al. 2003

View full text Add to dashboard Cite

Abstract-Biochemical and genetic evidence support the involvement of leukocyte-type 12/15-lipoxygenase enzyme and its products in the atherogenic process. We recently showed that products of the 12/15-lipoxygenase pathway play an important role in mediating hypertrophy, matrix protein production, and inflammatory gene expression in vascular smooth muscle cells (VSMC) through activation of mitogen activated protein kinases and key transcription factors. The current study is aimed at establishing the in vivo role of 12/15-lipoxygenase in VSMC by comparing growth factor-induced responses in VSMC derived from 12/15-lipoxygenase knockout mice versus genetic control wild-type mice. In the lipoxygenase knockout cells, 12/15-lipoxygenase protein was not expressed, and levels of its product, 12(S)-hydroxyeicosatetraenoic acid, were reduced (51% of wild type). Knockout cells exhibited significantly lower rates of growth factor-induced migration, fibronectin production, and incorporation of 3 H-thymidine and 3 H-leucine (54%, 55%, 61%, and 57% of wild type, respectively). Growth factor-induced superoxide production and p38 mitogen-activated protein kinase activation were also reduced in knockout cells. Serum-stimulated AP-1 transcription factor activation was markedly reduced (50% of wild type), whereas cAMP response element binding protein activation was abrogated in knockout cells. Furthermore, growth factor-induced mRNA expression of immediate early genes and fibronectin were also greatly reduced. These results suggest that the modulation of specific signaling pathways and growth-responsive genes may be responsible for the altered growth factor responses in the lipoxygenase knockout cells. Leukocyte-type 12-LO has a wide tissue distribution, including vascular smooth muscle cells (VSMC). 6,7 In mice, both leukocyte 12/15-LO and platelet 12-LO are expressed. 8 Studies indicate that LO inhibition reduced blood pressure in renovascular hypertensive rats. 9 Furthermore, 12(S)-HETE levels were elevated in spontaneously hypertensive rats compared with age-matched Wistar-Kyoto rats, and 12(S)-HETE directly regulated calcium signals in VSMC. 10,11 Several lines of evidence implicate 12/15-LO in the development of atherosclerosis. 12/15-LO can mediate the oxidation of LDL, 12 and the enzyme and its products have been detected in atherosclerotic lesions. 13,14 Convincing evidence comes from recent data showing that disruption of 12/15-LO in apoE Ϫ/Ϫ or LDL-R Ϫ/Ϫ mice significantly reduced atherosclerosis in these mice models. 15,16 Additionally, growth factors (GFs) such as angiotensin II (Ang II) and platelet-derived growth factor (PDGF) and cytokines such as IL-1, IL-4, and IL-8 could induce 12/15-LO activity and expression in VSMC. 7,[17][18][19] Furthermore, the 12-LO product 12(S)-HETE could induce VSMC migration and extracellular matrix production. 20,21 Ang II-induced hypertrophy as well as PDGF-induced chemotactic effects were significantly blocked by pharmacological LO inhibitors and a molecular inhibitor, 12-LO ribozyme...

show abstract

mentioning

confidence: 98%

Reduced Growth Factor Responses in Vascular Smooth Muscle Cells Derived from 12/15-Lipoxygenase–Deficient Mice

et al. 2003

View full text Add to dashboard Cite

show abstract

“…Increased formation of LO products such as 12(S)-HETE by the biological agents involved in cardiovascular dysfunction has been reported in VSMCs, endothelial cells, and monocytes (6,(13)(14)(15)22). 12(S)-HETE has direct effects like chemotaxis (23); changes in vascular tone (24); and production of vascular endothelial growth factor, a potent angiogenic agent (25). It can also induce monocyte binding to endothelial cells (22) and can mediate AngII-induced changes in neuronal K ϩ currents (26).…”

mentioning

confidence: 99%

The Oxidized Lipid and Lipoxygenase Product 12(S)-Hydroxyeicosatetraenoic Acid Induces Hypertrophy and Fibronectin Transcription in Vascular Smooth Muscle Cells via p38 MAPK and cAMP Response Element-binding Protein Activation

Reddy¹,

Thimmalapura²,

Lanting³

et al. 2002

Journal of Biological Chemistry

126

137

View full text Add to dashboard Cite

Growth factor-and cytokine-induced vascular smooth muscle cell proliferation, migration, hypertrophy, and matrix production have been shown to play important roles in the development of vascular disorders such as atherosclerosis, hypertension, and restenosis. Growth factors such as angiotensin II (AngII) 1 and platelet-derived growth factor (PDGF) activate intracellular phospholipases, leading to the formation of arachidonic acid, which can be further metabolized by cyclooxygenases, cytochrome P-450 oxygenases, and lipoxygenases (1). Lipoxygenase (LO) action leads to the formation of oxidized lipids such as 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE). LOs and their products of arachidonic acid and linoleic acid metabolism have been shown to mediate growth factor effects in vascular smooth muscle cells (VSMCs) as well as responses to vascular injury. Lipoxygenases are classified as 5-, 8-, 12-, and 15-lipoxygenases based on their ability to insert molecular oxygen at the corresponding carbon atom of arachidonic acid. Three major isoforms of 12-LO have been cloned. They are platelet-type 12-LO, leukocyte-type 12-LO, and epidermis-type 12-LO. These proteins are products of distinct genes and vary in tissue distribution (2, 3).Leukocyte 12-LO has been cloned from porcine and mouse leukocytes (4, 5). The presence of leukocyte-type 12-LO (also termed 12/15-LO) has also been demonstrated in various cell types and tissues, including VSMCs, adrenal cells, rat brain, and kidney (6 -11). Studies from this and other laboratories (12-21) have implicated the leukocyte-type 12-LO pathway in the pathogenesis of atherosclerosis and restenosis. 12-LO expression was demonstrated in atherosclerotic lesions (12). In vascular and mononuclear cells, growth factors and cytokines as well as high glucose stimulate both the activity and expression of 12-LO (6, 13-15). Furthermore, expression of 12-LO protein and mRNA is markedly increased in neointima of balloon-injured rat carotid arteries, and pretreatment with LO inhibitors reduces the rate of neointimal thickening in this model (16,17). We have demonstrated that treatment with a chimeric DNA-RNA hammerhead ribozyme targeted to cleave rat leukocyte-type 12-LO mRNA significantly reduces neointimal thickening in balloon-injured rat arteries (18). We have

show abstract

“…10 Earlier studies by us and others have shown that LO products have potent growth and chemotactic effects in VSMCs. 11,12 LO products could also mediate the growth and chemotactic effects of high glucose as well as that of growth factors, such as angiotensin II and platelet-derived growth factor. [12][13][14] However, the signal transduction pathways and gene regulation mechanisms initiated by the lipid peroxidation products of the LO pathway, such as 13-HPODE in VSMCs, are not clear.…”

mentioning

confidence: 99%

Signaling Mechanisms of Nuclear Factor-κB-Mediated Activation of Inflammatory Genes by 13-Hydroperoxyoctadecadienoic Acid in Cultured Vascular Smooth Muscle Cells

Natarajan

Reddy

Malik

et al. 2001

ATVB

View full text Add to dashboard Cite

Abstract-Oxidatively modified low density lipoprotein (LDL) has been implicated in the pathogenesis of atherosclerosis.LDL oxidation may be mediated by several factors, including cellular lipoxygenases. The lipoxygenase product of linoleic acid, 13-hydroperoxyoctadecadienoic acid (13-HPODE), is a significant component of oxidized LDL and has been shown to be present in atherosclerotic lesions. However, the mechanism of action of these oxidized lipids in vascular smooth muscle cells (VSMCs) is not clear. In the present study, we show that 13-HPODE leads to the activation of Ras as well as the mitogen-activated protein kinases, extracellular signal-regulated kinase 1/2, p38, and c-Jun amino-terminal kinase, in porcine VSMCs. 13-HPODE also specifically activated the oxidant stress-responsive transcription factor, nuclear factor-B, but not activator protein-1 or activator protein-2. 13-HPODE-induced nuclear factor-B DNA binding activity was blocked by an antioxidant, N-acetylcysteine, as well as an inhibitor of protein kinase C. 13-HPODE, but not the hydroxy product, 13-(S)-hydroxyoctadecadienoic acid, also dose-dependently increased vascular cell adhesion molecule-1 promoter activation. This was inhibited by an antioxidant as well as by inhibitors of Ras p38 mitogen-activated protein kinase and protein kinase C. Our results suggest that oxidized lipid components of oxidized LDL, such as 13-HPODE, may play a key role in the atherogenic process by inducing the transcriptional regulation of inflammatory genes in VSMCs via the activation of key signaling kinases. (Arterioscler Thromb

show abstract

Comparative effect of lipoxygenase products of arachidonic acid on rat aortic smooth muscle cell migration

Cited by 148 publications

References 11 publications

Reduced Growth Factor Responses in Vascular Smooth Muscle Cells Derived from 12/15-Lipoxygenase–Deficient Mice

Reduced Growth Factor Responses in Vascular Smooth Muscle Cells Derived from 12/15-Lipoxygenase–Deficient Mice

The Oxidized Lipid and Lipoxygenase Product 12(S)-Hydroxyeicosatetraenoic Acid Induces Hypertrophy and Fibronectin Transcription in Vascular Smooth Muscle Cells via p38 MAPK and cAMP Response Element-binding Protein Activation

Signaling Mechanisms of Nuclear Factor-κB-Mediated Activation of Inflammatory Genes by 13-Hydroperoxyoctadecadienoic Acid in Cultured Vascular Smooth Muscle Cells

Contact Info

Product

Resources

About