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Lipid second messengers and cell signaling in vascular wall

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Abstract

Agonists of cellular receptors, such as receptor tyrosine kinases, G protein-coupled receptors, cytokine receptors, etc., activate phospholipases (Cγ, Cβ, A2, D), sphingomyelinase, and phosphatidylinositol-3-kinase. This produces active lipid metabolites, some of which are second messengers: inositol trisphosphate, diacylglycerides, ceramide, and phosphatidylinositol 3,4,5-trisphosphate. These universal mechanisms are involved in signal transduction to maintain blood vessel functions: regulation of vasodilation and vasoconstriction, mechanical stress resistance, and anticoagulant properties of the vessel lumen surface. Different signaling pathways realized through lipid second messengers interact to one another and modulate intracellular events. In early stages of atherogenesis, namely, accumulation of low density lipoproteins in the vascular wall, cascades of pro-atherogenic signal transduction are triggered through lipid second messengers. This leads to atherosclerosis, the general immuno-inflammatory disease of the vascular system.

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Abbreviations

AT1 :

angiotensin II receptor

cPLA2 :

cytosolic phospholipase A2

DAG:

diacylglycerides

eNOS:

endothelial NO synthase

ERK:

extracellular signal-regulated kinases

ET-1:

endothelin-1

FAK:

focal adhesion kinase

HDL:

high density lipoproteins

IP3 :

inositol trisphosphate

LDL:

low density lipoproteins

MAPK:

mitogen-activated protein kinases

MLC:

myosin light chains

oxLDL:

oxidized LDL

PDGF:

platelet-derived growth factor

PI3K:

phosphatidylinositol 3-kinase

PKB:

protein kinase B/Akt

PKC:

protein kinase C

PLA2 :

phospholipase A2

PLD:

phospholipase D

PtdIns(3)P:

phosphatidylinositol 3-monophosphate

PtdIns(3,4)P2 :

phos-phatidylinositol 3,4-bisphosphate

PtdIns(3,5)P2 :

phos-phatidylinositol 3,5-bisphosphate

PtdIns(4,5)P2 :

phos-phatidylinositol 4,5-bisphosphate

PtdIns(3,4,5)P3 :

phos-phatidylinositol 3,4,5-trisphosphate

ROS:

reactive oxygen species

SAPK:

stress-activated protein kinase

SMC:

smooth muscle cells

S1P:

sphingosine-1-phosphate

TGF-β:

trans-forming growth factor-β

TNF-α:

tumor necrosis factor-α

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  1. Institute of Experimental Cardiology, Russian Cardiology Research Center, 3-ya Cherepkovskaya ul. 15a, 121552, Moscow, Russia

    N. V. Prokazova, N. N. Samovilova, N. K. Golovanova, E. V. Gracheva, A. A. Korotaeva & E. R. Andreeva

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  1. N. V. Prokazova
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  2. N. N. Samovilova
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Original Russian Text © N. V. Prokazova, N. N. Samovilova, N. K. Golovanova, E. V. Gracheva, A. A. Korotaeva, E. R. Andreeva, 2007, published in Biokhimiya, 2007, Vol. 72, No. 8, pp. 981–994.

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Prokazova, N.V., Samovilova, N.N., Golovanova, N.K. et al. Lipid second messengers and cell signaling in vascular wall. Biochemistry Moscow 72, 797–808 (2007). https://doi.org/10.1134/S0006297907080019

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