Vascular smooth muscle cells preloaded with eicosapentaenoic acid and docosahexaenoic acid fail to respond to serotonin stimulation

Pakala, Rajbabu; Pakala, Rajashree; Sheng, Wen Lu; Benedict, Claude R.

doi:10.1016/s0021-9150(00)00392-0

Cited by 17 publications

(20 citation statements)

References 60 publications

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“…17,18 EPA and DHA have also been shown to block the mitogenic effect of growth factors that act through receptor tyrosine kinase (such as platelet derived growth factor, fibroblast growth factor, epidermal growth factor, insulin-like growth factor) and G-proteincoupled receptors (such as bomberin, bradykinin, vasopressin, thrombin, serotonin, and thromboxane A2) signaling pathways. 12,13 Polyunsaturated fatty acids also regulate key genes related to hepatic lipid metabolism. 22,23 Whether the effects of n-3 or the n-3/n-6 fatty acid balance on neural function or other aspects of growth and development are mediated through regulatory effects on gene expression is an important area for further study.…”

Section: Polyunsaturated Fatty Acid Metabolismmentioning

confidence: 99%

“…[3][4][5][6][7][8] Changes in cognitive performance and behavior and the transmission of visual and auditory information could involve the effects of DHA on neurotransmitter metabolism, ion channel activity, signaling pathways, or gene expression. [9][10][11][12][13][14][15][16][17][18] ARA is essential for normal growth and is critically important through its role in cell signaling and as a precursor to series 2 eicosanoids and series 3 leukotrienes, which also play a role in synaptic transmission. [19][20][21] The action of n-6 and n-3 fatty acids on metabolic and physiologic pathways may involve 3 general mechanisms: membrane phospholipid fatty acids influence the properties of the microenvironment of membrane bilayers and this in turn can effect the activity of membrane-associated proteins, receptors, transport systems, and ion channels; membrane phospholipids and their n-6 and n-3 fatty acids function as signal molecules and as precursors for eicosanoids; and finally, the n-6 and n-3 fatty acids have rapid and direct effects on gene expression through peroxisome proliferator activated receptor (PPAR)-dependent and PPAR-independent mechanisms.…”

mentioning

confidence: 99%

“…[19][20][21] The action of n-6 and n-3 fatty acids on metabolic and physiologic pathways may involve 3 general mechanisms: membrane phospholipid fatty acids influence the properties of the microenvironment of membrane bilayers and this in turn can effect the activity of membrane-associated proteins, receptors, transport systems, and ion channels; membrane phospholipids and their n-6 and n-3 fatty acids function as signal molecules and as precursors for eicosanoids; and finally, the n-6 and n-3 fatty acids have rapid and direct effects on gene expression through peroxisome proliferator activated receptor (PPAR)-dependent and PPAR-independent mechanisms. [12][13][14][15][16][17][18][19]22,23 Deficiency of key components for normal growth and development, as illustrated for example by iron or iodine deficiency, during key stages of development can have longterm consequences for neural development in infants and children. 24,25 The difference in dietary intake of DHA and ARA among infants fed milk and formula diets 26 and their important role in visual and neural function has focused attention on the need to elucidate the ability of infants to form ARA and DHA from their LA and LNA precursors, respectively, the pathways by which these fatty acids are transferred to the developing brain and retina, and the effects of n-6 and n-3 fatty acid nutrition on infant growth and visual and neural development.…”

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confidence: 99%

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Perinatal biochemistry and physiology of long-chain polyunsaturated fatty acids

Innis

2003

The Journal of Pediatrics

429

287

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Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are important structural components of the central nervous system. These fatty acids are transferred across the placenta, are present in human milk, and are accumulated in the brain and retina during fetal and infant development. The high concentrations of DHA in the retina and of DHA and ARA in brain gray matter suggests that these fatty acids have important roles in retinal and neural function. Animal studies have shown that depletion of DHA from the retina and brain results in reduced visual function and learning deficits. The latter effects may be explained by changes in the membrane bilayer that alter membrane-associated receptors and signal transduction systems, ion channel activity, or direct effects on gene expression. DHA can be formed in the liver from alpha linolenic acid, but it is unclear if the rate of DHA synthesis in humans is sufficient to support optimal brain and retinal development. Although there is no evidence that the ability to form ARA from linoleic acid is limiting, supplementation with DHA reduces tissue ARA, possibly creating a conditional need for ARA in infants with a dietary intake of DHA. The amount of DHA in human milk varies widely and is positively correlated with visual and language development in breast-fed infants. Advances in understanding essential fatty acid requirements will benefit from intervention studies that use functionally relevant tests to probe the deficiency or adequacy of physiologically important pools of DHA and ARA in developing infants. (J Pediatr 2003;143:S1-S8) D ocosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (ARA, 20:4n-6) are important structural components of the highly specialized membranes lipids of the human central nervous system. 1,2 DHA is the major polyunsaturated fatty acid in the outer segments of the retina rods and cones, where it can constitute as much as 50% of the fatty acids in phosphatidylethanolamine (PE) and phosphatidylserine (PS), and as much as 80% of all the polyunsaturated fatty acids.1 These membranes are specialized for the rapid transmission of light and contain 90% to 95% of the lipid as phospholipid. The phospholipids contain unusual PE, PS, and phosphatidylcholine (PC) species in which both acyl groups are DHA. Approximately 10% of the weight of the brain, and 50% of the dry weight, is lipid. About half of this lipid is phospholipid, with approximately 20% cholesterol, 15% to 20% cerebrosides, and smaller amounts of sulphatides and gangliosides.2 The phospholipids of brain gray matter contain high proportions of DHA in PE and PS and high amounts of ARA in phosphatidylinositol (PI). ARA is also present in membrane phospholipids, particularly in PI throughout the body. Unlike other organs, the dietary essential fatty acid linoleic acid (LA, 18:2n-6) usually represents <1% of brain and retina fatty acids, and concentrations of a-linolenic acid (18:3n-3) are even lower. 2These usual characteristics of brain and retina phospholipids suggest that specific mechanisms ...

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Section: Polyunsaturated Fatty Acid Metabolismmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Perinatal biochemistry and physiology of long-chain polyunsaturated fatty acids

Innis

2003

The Journal of Pediatrics

429

287

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“…Further analyses suggest that balance between n-3 and n-6 PUFAs may also be critical in regulating inflammation (11,12). EPA and DHA may help protect against atherosclerosis by inhibiting the proliferation of SMCs (13,14) or by causing apoptosis (15).…”

mentioning

confidence: 99%

Different effects of n-6 and n-3 polyunsaturated fatty acids on the activation of rat smooth muscle cells by interleukin-1β

Bousserouel¹,

Brouillet²,

Béréziat³

et al. 2003

Journal of Lipid Research

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There is good evidence that the n-3 polyunsaturated fatty acids (PUFAs) in fish oil have antiinflammatory effects and reduce the pathogenesis of atherosclerosis. However, the mechanisms underlying these actions are largely unknown. This study was designed to investigate the effects of membrane incorporation of two major components of fish oil [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)], on rat smooth muscle cells (SMCs) activation induced by interleukin-1 ␤ (IL1 ␤ ). We compared their effects with those of n-6 arachidonic acid (AA). Expression of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1 adhesion molecules involved in SMCs migration was enhanced by AA, whereas EPA and DHA had no similar effects. We established that AA potentiates IL1 ␤ -induced expression of the type IIA secreted phospholipase A2 (sPLA2) gene, whereas EPA and DHA reduce this stimulation. EPA and DHA also abolished proinflammatory prostaglandin PGE2 production by inhibiting the IL1 ␤ -induced production of cyclooxygenase-2 (COX-2) mRNA. Much interest was then focused on three transcriptional factors implicated in inflammation control and especially in modulating rat sPLA2 and COX-2 gene transcription: nuclear factor-B, CCAAT/enhancer binding protein ␤ , and E26 transformation-specific-1. electrophoretic mobility shift assay revealed that the binding activity of all three factors was increased by AA and reduced (or not affected) by n-3 PUFA. These results indicate that EPA and DHA act in opposition to AA by modulating various steps of the inflammatory process induced by IL1 ␤ , probably by reducing mitogen-activated protein kinase p42/p44 activity. -Bousserouel, S., A. Brouillet, G. Béréziat, M. Raymondjean, and M. Andréani. Different effects of n-6 and n-3 polyunsaturated fatty acids on the activation of rat smooth muscle cells by interleukin-1 ␤ . J. Lipid Res. 2003. 44: 601-611.

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“…Another potential mechanism by which fish oils may prevent the development of atherosclerosis or restenosis could be inhibition of the mitogen induced smooth muscle cell (SMC) proliferation and migration of these into the vessel wall intima [73,74]. Pakala et al [75] in cell culture showed that EPA and DHA inhibit smooth muscle cells proliferation induce by serotonin (5HT) and thromboxane A 2 .…”

Section: Molecular Mechanism Of N-3 Fa Related To Cvdmentioning

confidence: 99%