Oxidized low-density lipoprotein (LDL) enhances thromboxane A2 synthesis by platelets, but lysolecithin as a product of LDL oxidation has an inhibitory effect

Mahfouz, Mahmoud; Kummerow, Fred A.

doi:10.1016/s0090-6980(00)00078-2

Cited by 14 publications

(8 citation statements)

References 55 publications

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“…This response then faded as the oxLDL concentration increased, suggesting the additional presence of a less potent antagonist(s). One lipid of oxLDL that can interfere with platelet function is lysophosphatidylcholine9, 44, but its role is enigmatic. Its actions are concentration dependent, either aiding or suppressing platelet function, and acts in receptor dependent and independent ways.…”

Section: Discussionmentioning

confidence: 99%

Platelet Activation by Low Concentrations of Intact Oxidized LDL Particles Involves the PAF Receptor

Chen

Salomon

et al. 2009

ATVB

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Objective-Mitochondrial depolarization aids platelet activation. Oxidized LDL (oxLDL) contains the medium length oxidatively truncated phospholipid hexadecyl azelaoyl-lysoPAF (HAz-LPAF) that disrupts mitochondrial function in nucleated cells, so oxLDL may augment platelet activation. Methods and Results-Flow cytometry showed intact oxLDL particles synergized with subthreshold amounts of soluble agonists to increase intracellular Ca 2ϩ , and initiate platelet aggregation and surface expression of activated gpIIb/IIIa and P-selectin. oxLDL also induced aggregation and increased intracellular Ca 2ϩ in FURA2-labeled cells by itself at low, although not higher, concentrations. HAz-LPAF, alone and in combination with substimulatory amounts of thrombin, rapidly increased cytoplasmic Ca 2ϩ and initiated aggregation. HAz-LPAF depolarized mitochondria in intact platelets, but this required concentrations beyond those that directly activated platelets. An unexpectedly large series of chemically pure truncated phospholipids generated by oxidative fragmentation of arachidonoyl-, docosahexaneoyl-, or linoleoyl alkyl phospholipids were platelet agonists. The PAF receptor, thought to effectively recognize only phospholipids with very short sn-2 residues, was essential for platelet activation because PAF receptor agonists blocked signaling by all these medium length phospholipids and oxLDL. Key Words: oxidized LDL Ⅲ PAF Ⅲ platelet Ⅲ phospholipid Ⅲ PAF acetylhydrolase P latelet mitochondria maintain cellular energetics and viability, 1 but these organelles also affect platelet activation. Thrombin produces a rapid decrease in mitochondrial transmembrane potential, thereby increasing reactive oxygen specie formation and caspase 3 activation needed for maximal aggregation. 2 Combining maximal amounts of thrombin with collagen 3 or with activators of Bax, 4 a proapoptotic protein that physically targets mitochondria, generates a subpopulation of highly activated platelets, and blockade of the mitochondrial permeability transition pore suppresses this form of platelet activation. 5,6 Oxidized low density lipoprotein (oxLDL) has a fundamental role in thrombotic disease and atherogenesis through activation of inflammatory cells that includes platelets, 7,8 although the identity of the agonist(s) is unclear because oxLDL contains numerous bioactive compounds. 9 Oxidation of lipoprotein particles, either chemically or enzymatically, 10,11 fragments phospholipids that contain polyunsaturated fatty acyl residues. One such oxidatively-truncated phospholipid, hexadecyl azelaoyl lysoPAF (HAz-LPAF), derived from oxidation of common linoleoyl residues, rapidly enters nucleated cells, traffics to mitochondria, and initiates the mitochondrial-dependent pathway to apoptotic cell death. 12 We determined whether oxidized LDL contains agents that disrupt platelet mitochondrial function, thereby increasing cellular responsiveness. We prepared pure samples of a series of fragmented alkyl glycerophosphocholines-acylated lysoPAFs-found in oxidized LD...

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Section: Discussionmentioning

confidence: 99%

Platelet Activation by Low Concentrations of Intact Oxidized LDL Particles Involves the PAF Receptor

Chen

Salomon

et al. 2009

ATVB

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“…They inhibited cyclooxygenase, an enzyme required for the conversion of arachidonic acid to prostacyclin, a molecule which prevents blood clots [43]. Moreover, oxidized fat enhanced thromboxane synthesis [44,45], which caused the formation of a blood clot. Trans fatty acids in partially hydrogenated vegetable oil decreased pros-tacyclin synthesis by inhibiting cyclooxygenase.…”

Section: The Trans Fatty Acids In Partially Hydrogenated Fat Can Causmentioning

confidence: 99%

The Effects of Hydrogenation on Soybean Oil

Kummerow¹

2013

Soybean - Bio-Active Compounds

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“…It was concluded that the effects of LPC on platelet function were due to structural modifi cation of the platelet membrane probably by its amphiphilic properties [69,70] . In later studies, LPC-mediated platelet inhibition was related to the G-protein mediated activation of adenylate cyclase, or to the incorporation of LPC into the platelet membrane leading to changes of membrane fl uidity [71,72] . Another study found that incubation of washed platelets with low concentrations of LPC (10 M ) could stimulate P-selectin expression through a protein kinase C-dependent pathway [73] .…”

Section: Action Of Lpc On Plateletsmentioning

confidence: 99%

Platelet Interaction with Bioactive Lipids Formed by Mild Oxidation of Low-Density Lipoprotein

Siess¹

2006

Pathophysiol Haemos Thromb

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Oxidized low-density lipoprotein (LDL) enhances thromboxane A2 synthesis by platelets, but lysolecithin as a product of LDL oxidation has an inhibitory effect

Cited by 14 publications

References 55 publications

Platelet Activation by Low Concentrations of Intact Oxidized LDL Particles Involves the PAF Receptor

Platelet Activation by Low Concentrations of Intact Oxidized LDL Particles Involves the PAF Receptor

The Effects of Hydrogenation on Soybean Oil

Platelet Interaction with Bioactive Lipids Formed by Mild Oxidation of Low-Density Lipoprotein

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