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Oxidized LDL activates blood platelets through
CD36/NOX2–mediated inhibition of the cGMP/protein
kinase G signaling cascade
by Simbarashe Magwenzi, Casey Woodward, Katie S. Wraith, Ahmed Aburima,
Zaher Raslan, Huw Jones, Catriona McNeil, Stephen Wheatcroft, Nadira
Yuldasheva, Maria Febbriao, Mark Kearney, and Khalid M. Naseem
Blood
Volume 125(17):2693-2703
April 23, 2015
©2015 by American Society of Hematology
oxLDL stimulates ROS production in platelets.
Simbarashe Magwenzi et al. Blood 2015;125:2693-2703
©2015 by American Society of Hematology
oxLDL stimulates platelet ROS production in a CD36- and NOX2-dependent manner.
Simbarashe Magwenzi et al. Blood 2015;125:2693-2703
©2015 by American Society of Hematology
oxLDL-induced ROS generation and activation of gp91phox/NOX2 requires PKC. (A) Washed
human platelets incubated with apyrase, indomethacin, and EGTA were treated with PP2 and
PP3 and then with LDL before being lysed with ice-cold lysis buffer.26 Lysates wer...
Simbarashe Magwenzi et al. Blood 2015;125:2693-2703
©2015 by American Society of Hematology
oxLDL modulates cGMP-mediated inhibition of platelet aggregation and arrest under conditions
of flow.
Simbarashe Magwenzi et al. Blood 2015;125:2693-2703
©2015 by American Society of Hematology
oxLDL inhibits cGMP signaling through a mechanism that requires CD36, Src kinases, and PKC.
(A) Human platelets (3 × 108 platelets/mL) were incubated with nLDL (50 µg/mL), oxLDL (50
µg/ml), oxPCCD36 (5 µmol/L), or PAPC (5 µmol/L) prior to the addition of 8-...
Simbarashe Magwenzi et al. Blood 2015;125:2693-2703
©2015 by American Society of Hematology
oxLDL inhibits cGMP-signaling through a mechanism that requires NOX2 and intracellular ROS.
(A) Platelets (5 × 108 platelets/mL) were incubated with apyrase (2 U/mL), indomethacin (10
µmol/L), and EGTA (1 mmol/L) and treated with MnTMPyP (100 µmol/L) or TEM...
Simbarashe Magwenzi et al. Blood 2015;125:2693-2703
©2015 by American Society of Hematology
oxLDL and hyperlipidemia caused decreased platelet sensitivity to cGMP through NOX2.
Simbarashe Magwenzi et al. Blood 2015;125:2693-2703
©2015 by American Society of Hematology
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