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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.

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Presentation on theme: "Oxidized LDL activates blood platelets through CD36/NOX2–mediated inhibition of the cGMP/protein kinase G signaling cascade by Simbarashe Magwenzi, Casey."— Presentation transcript:

1 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

2 oxLDL stimulates ROS production in platelets. Simbarashe Magwenzi et al. Blood 2015;125:2693-2703 ©2015 by American Society of Hematology

3 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

4 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

5 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

6 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

7 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

8 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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