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Protein Kinase A Regulates Platelet Phosphodiesterase 3A through an A-Kinase Anchoring Protein Dependent Manner (2024)
Journal Article
Khalil, J. S., Law, R., Raslan, Z., Cheah, L. T., Hindle, M. S., Aburima, A. A., Kearney, M. T., & Naseem, K. M. (2024). Protein Kinase A Regulates Platelet Phosphodiesterase 3A through an A-Kinase Anchoring Protein Dependent Manner. Cells, 13(13), Article 1104. https://doi.org/10.3390/cells13131104

Platelet activation is critical for haemostasis, but if unregulated can lead to pathological thrombosis. Endogenous platelet inhibitory mechanisms are mediated by prostacyclin (PGI2)-stimulated cAMP signalling, which is regulated by phosphodiesterase... Read More about Protein Kinase A Regulates Platelet Phosphodiesterase 3A through an A-Kinase Anchoring Protein Dependent Manner.

Thrombospondin-1 promotes hemostasis through modulation of cAMP signaling in blood platelets (2020)
Journal Article
Aburima, A., Berger, M., Spurgeon, B. E., Webb, B. A., Wraith, K. S., Febbraio, M., Poole, A. W., & Naseem, K. M. (2021). Thrombospondin-1 promotes hemostasis through modulation of cAMP signaling in blood platelets. Blood, 137(5), 678-689. https://doi.org/10.1182/blood.2020005382

Thrombospondin-1 (TSP-1) is released by platelets upon activation and can increase platelet activation, but its role in hemostasis in vivo is unclear. We show that TSP-1 is a critical mediator of hemostasis that promotes platelet activation by modula... Read More about Thrombospondin-1 promotes hemostasis through modulation of cAMP signaling in blood platelets.

Author Correction: Effect of induced hypoglycemia on inflammation and oxidative stress in type 2 diabetes and control subjects (Scientific Reports, (2020), 10, 1, (4750), 10.1038/s41598-020-61531-z) (2020)
Journal Article
Kahal, H., Halama, A., Aburima, A., Bhagwat, A. M., Butler, A. E., Graumann, J., Suhre, K., Sathyapalan, T., & Atkin, S. L. (2020). Author Correction: Effect of induced hypoglycemia on inflammation and oxidative stress in type 2 diabetes and control subjects (Scientific Reports, (2020), 10, 1, (4750), 10.1038/s41598-020-61531-z). Scientific reports, 10(1), Article 10233. https://doi.org/10.1038/s41598-020-66189-1

© 2020, The Author(s). The original version of this Article contained a typographical error in the spelling of the author Johannes Graumann, which was incorrectly given as Johannes Grauman. This has now been corrected in the PDF and HTML versions of... Read More about Author Correction: Effect of induced hypoglycemia on inflammation and oxidative stress in type 2 diabetes and control subjects (Scientific Reports, (2020), 10, 1, (4750), 10.1038/s41598-020-61531-z).

Effect of induced hypoglycemia on inflammation and oxidative stress in type 2 diabetes and control subjects (2020)
Journal Article
Kahal, H., Halama, A., Aburima, A., Bhagwat, A. M., Butler, A. E., Grauman, J., Suhre, K., Sathyapalan, T., & Atkin, S. L. (2020). Effect of induced hypoglycemia on inflammation and oxidative stress in type 2 diabetes and control subjects. Scientific reports, 10(1), Article 4750. https://doi.org/10.1038/s41598-020-61531-z

Intensive diabetes control has been associated with increased mortality in type 2 diabetes (T2DM); this has been suggested to be due to increased hypoglycemia. We measured hypoglycemia-induced changes in endothelial parameters, oxidative stress marke... Read More about Effect of induced hypoglycemia on inflammation and oxidative stress in type 2 diabetes and control subjects.

Atherogenic lipid stress induces platelet hyperactivity through CD36-mediated hyposensitivity to prostacyclin-; the role of phosphodiesterase 3A. (2019)
Journal Article
Berger, M., Raslan, Z., Aburima, A., Magwenzi, S., Wraith, K. S., Spurgeon, B. E., Hindle, M. S., Law, R., Febbraio, M., & Naseem, K. M. (2020). Atherogenic lipid stress induces platelet hyperactivity through CD36-mediated hyposensitivity to prostacyclin-; the role of phosphodiesterase 3A. Haematologica, 105(3), 808-819. https://doi.org/10.3324/haematol.2018.213348

©2020 Ferrata Storti Foundation Prostacyclin (PGI2) controls platelet activation and thrombosis through a cyclic adenosine monophosphate (cAMP) signaling cascade. However, in patients with cardiovascular diseases this protective mechanism fails for r... Read More about Atherogenic lipid stress induces platelet hyperactivity through CD36-mediated hyposensitivity to prostacyclin-; the role of phosphodiesterase 3A..

Alterations in platelet alpha-granule secretion and adhesion on collagen under flow in mice lacking the atypical rho GTPase RhoBTB3 (2019)
Journal Article
Berger, M., Riley, D. R. J., Lutz, J., Khalil, J. S., Aburima, A., Naseem, K. M., & Rivero, F. (2019). Alterations in platelet alpha-granule secretion and adhesion on collagen under flow in mice lacking the atypical rho GTPase RhoBTB3. Cells, 8(2), Article 149. https://doi.org/10.3390/cells8020149

Typical Rho GTPases, such as Rac1, Cdc42, and RhoA, act as molecular switches regulating various aspects of platelet cytoskeleton reorganization. The loss of these enzymes results in reduced platelet functionality. Atypical Rho GTPases of the RhoBTB... Read More about Alterations in platelet alpha-granule secretion and adhesion on collagen under flow in mice lacking the atypical rho GTPase RhoBTB3.

Dyslipidemia-associated atherogenic oxidized lipids induce platelet hyperactivity through phospholipase Cγ2-dependent reactive oxygen species generation (2018)
Journal Article
Berger, M., Wraith, K., Woodward, C., Aburima, A., Raslan, Z., Hindle, M. S., …Naseem, K. M. (2019). Dyslipidemia-associated atherogenic oxidized lipids induce platelet hyperactivity through phospholipase Cγ2-dependent reactive oxygen species generation. Platelets, 30(4), 467-472. https://doi.org/10.1080/09537104.2018.1466386

Oxidized low-density lipoprotein (oxLDL) and associated oxidized phosphocholine-headgroup phospholipids (oxPCs) activate blood platelets through ligation of the scavenger receptor CD36. Previously, we found that oxLDL stimulated phosphorylation of ph... Read More about Dyslipidemia-associated atherogenic oxidized lipids induce platelet hyperactivity through phospholipase Cγ2-dependent reactive oxygen species generation.

Platelet function following induced hypoglycaemia in type 2 diabetes (2018)
Journal Article
Kahal, H., Aburima, A., Spurgeon, B., Wraith, K. S., Rigby, A. S., Sathyapalan, T., Kilpatrick, E. S., Naseem, K. M., & Atkin, S. L. (2018). Platelet function following induced hypoglycaemia in type 2 diabetes. Diabetes & metabolism, 44(5), 431-436. https://doi.org/10.1016/j.diabet.2018.04.004

Aim
Strict glycaemic control has been associated with an increased mortality rate in subjects with type 2 diabetes (T2DM). Here we examined platelet function immediately and 24 hours following induced hypoglycaemia in people with type 2 diabetes comp... Read More about Platelet function following induced hypoglycaemia in type 2 diabetes.

cGMP signaling inhibits platelet shape change through regulation of the RhoA-Rho Kinase-MLC phosphatase signaling pathway (2017)
Journal Article
Aburima, A., Walladbegi, K., Wake, J. D., & Naseem, K. M. (2017). cGMP signaling inhibits platelet shape change through regulation of the RhoA-Rho Kinase-MLC phosphatase signaling pathway. Journal of thrombosis and haemostasis : JTH, 15(8), 1668-1678. https://doi.org/10.1111/jth.13738

Essentials
Platelet shape change requires cytoskeletal rearrangement via myosin‐mediated actin contraction.
We investigated whether nitric oxide (NO) affected thrombin‐induced platelet shape change.
NO inhibits shape change, RhoA/ROCK signalling a... Read More about cGMP signaling inhibits platelet shape change through regulation of the RhoA-Rho Kinase-MLC phosphatase signaling pathway.

Prostacyclin reverses platelet stress fibre formation causing platelet aggregate instability (2017)
Journal Article
Yusuf, M. Z., Raslan, Z., Atkinson, L., Aburima, A., Thomas, S. G., Naseem, K. M., & Calaminus, S. D. (2017). Prostacyclin reverses platelet stress fibre formation causing platelet aggregate instability. Scientific reports, 7(1), Article ARTN 5582. https://doi.org/10.1038/s41598-017-05817-9

Prostacyclin (PGI2) modulates platelet activation to regulate haemostasis. Evidence has emerged to suggest that thrombi are dynamic structures with distinct areas of differing platelet activation. It was hypothesised that PGI2 could reverse platelet... Read More about Prostacyclin reverses platelet stress fibre formation causing platelet aggregate instability.

Targeting of type I protein kinase A to lipid rafts is required for platelet inhibition by the 3′,5′-cyclic adenosine monophosphate-signaling pathway (2015)
Journal Article
Raslan, Z., Magwenzi, S., Aburima, A., Taskén, K., & Naseem, K. M. (2015). Targeting of type I protein kinase A to lipid rafts is required for platelet inhibition by the 3′,5′-cyclic adenosine monophosphate-signaling pathway. Journal of thrombosis and haemostasis : JTH, 13(9), 1721-1734. https://doi.org/10.1111/jth.13042

Background Platelet adhesion to von Willebrand factor (VWF) is modulated by 3′,5′-cyclic adenosine monophosphate (cAMP) signaling through protein kinase A (PKA)-mediated phosphorylation of glycoprotein (GP)Ibβ. A-kinase anchoring proteins (AKAPs) are... Read More about Targeting of type I protein kinase A to lipid rafts is required for platelet inhibition by the 3′,5′-cyclic adenosine monophosphate-signaling pathway.

Oxidized LDL activates blood platelets through CD36/NOX2–mediated inhibition of the cGMP/protein kinase G signaling cascade (2015)
Journal Article
Magwenzi, S., Woodward, C., Wraith, K. S., Aburima, A., Raslan, Z., Jones, H., McNeil, C., Wheatcroft, S., Yuldasheva, N., Febbriao, M., Kearney, M., & Naseem, K. M. (2015). Oxidized LDL activates blood platelets through CD36/NOX2–mediated inhibition of the cGMP/protein kinase G signaling cascade. Blood, 125(17), 2693-2703. https://doi.org/10.1182/blood-2014-05-574491

Oxidized low-density lipoprotein (oxLDL) promotes unregulated platelet activation in dyslipidemic disorders. Although oxLDL stimulates activatory signaling, it is unclear how these events drive accelerated thrombosis. Here, we describe a mechanism fo... Read More about Oxidized LDL activates blood platelets through CD36/NOX2–mediated inhibition of the cGMP/protein kinase G signaling cascade.

Multiplexed phosphospecific flow cytometry enables large-scale signaling profiling and drug screening in blood platelets (2014)
Journal Article
Spurgeon, B. E., Aburima, A., Oberprieler, N. G., Taskén, K., & Naseem, K. M. (2014). Multiplexed phosphospecific flow cytometry enables large-scale signaling profiling and drug screening in blood platelets. Journal of thrombosis and haemostasis : JTH, 12(10), 1733-1743. https://doi.org/10.1111/jth.12670

Background: Dissecting the signaling events that contribute to platelet activation will increase our understanding of platelet function and aid in the development of new antiplatelet agents. However, high-throughput methodology for the quantitative a... Read More about Multiplexed phosphospecific flow cytometry enables large-scale signaling profiling and drug screening in blood platelets.

Acute hypertriglyceridemia induces platelet hyperactivity that is not attenuated by insulin in polycystic ovary syndrome. (2014)
Journal Article
Aye, M. M., Kilpatrick, E. S., Aburima, A., Wraith, K. S., Magwenzi, S., Spurgeon, B., …Atkin, S. L. (2014). Acute hypertriglyceridemia induces platelet hyperactivity that is not attenuated by insulin in polycystic ovary syndrome. Journal of the American Heart Association, 3(1), https://doi.org/10.1161/JAHA.113.000706

Atherothrombosis is associated with platelet hyperactivity. Hypertriglyceridemia and insulin resistance (IR) are features of polycystic ovary syndrome (PCOS). The effect of induced hypertriglyceridemia on IR and platelet function was examined in youn... Read More about Acute hypertriglyceridemia induces platelet hyperactivity that is not attenuated by insulin in polycystic ovary syndrome..

cAMP signaling regulates platelet myosin light chain (MLC) phosphorylation and shape change through targeting the RhoA-Rho kinase-MLC phosphatase signaling pathway (2013)
Journal Article
Aburima, A., Wraith, K. S., Raslan, Z., Law, R., Magwenzi, S., & Naseem, K. M. (2013). cAMP signaling regulates platelet myosin light chain (MLC) phosphorylation and shape change through targeting the RhoA-Rho kinase-MLC phosphatase signaling pathway. Blood, 122(20), 3533-3545. https://doi.org/10.1182/blood-2013-03-487850

Cyclic adenosine monophosphate (cAMP)-dependent signaling modulates platelet shape change through unknown mechanisms. We examined the effects of cAMP signaling on platelet contractile machinery. Prostaglandin E1 (PGE1)-mediated inhibition of thrombin... Read More about cAMP signaling regulates platelet myosin light chain (MLC) phosphorylation and shape change through targeting the RhoA-Rho kinase-MLC phosphatase signaling pathway.

Oxidized low-density lipoproteins induce rapid platelet activation and shape change through tyrosine kinase and Rho kinase–signaling pathways (2013)
Journal Article
Wraith, K. S., Magwenzi, S., Aburima, A., Wen, Y., Leake, D., & Naseem, K. (2013). Oxidized low-density lipoproteins induce rapid platelet activation and shape change through tyrosine kinase and Rho kinase–signaling pathways. Blood, 122(4), 580-589. https://doi.org/10.1182/blood-2013-04-491688

Oxidized low-density lipoproteins (oxLDL) generated in the hyperlipidemic state may contribute to unregulated platelet activation during thrombosis. Although the ability of oxLDL to activate platelets is established, the underlying signaling mechanis... Read More about Oxidized low-density lipoproteins induce rapid platelet activation and shape change through tyrosine kinase and Rho kinase–signaling pathways.

Polycystic ovary syndrome has no independent effect on vascular, inflammatory or thrombotic markers when matched for obesity (2013)
Journal Article
Kahal, H., Aburima, A., Ungvari, T., Rigby, A. S., Dawson, A. J., Coady, A. M., Vince, R. V., Ajjan, R. A., Kilpatrick, E. S., Naseem, K. M., & Atkin, S. L. (2013). Polycystic ovary syndrome has no independent effect on vascular, inflammatory or thrombotic markers when matched for obesity. Clinical Endocrinology, 79(2), 252-258. https://doi.org/10.1111/cen.12137

Introduction Previous studies investigating cardiovascular (CV) risk in obese women with polycystic ovary syndrome (PCOS) have been potentially confounded by not adequately accounting for body weight. Objective To assess if PCOS increases CV risk ind... Read More about Polycystic ovary syndrome has no independent effect on vascular, inflammatory or thrombotic markers when matched for obesity.

Thrombospondin-1 induces platelet activation through CD36-dependent inhibition of the cAMP/protein kinase A signaling cascade (2010)
Journal Article
Roberts, W., Magwenzi, S., Aburima, A., & Naseem, K. (2010). Thrombospondin-1 induces platelet activation through CD36-dependent inhibition of the cAMP/protein kinase A signaling cascade. Blood, 116(20), 4297-4306. https://doi.org/10.1182/blood-2010-01-265561

Cyclic adenosine monophosphate (cAMP)-dependent signaling modulates platelet function at sites of vascular injury. Here we show that thrombospondin-1 (TSP-1) prevents cAMP/protein kinase A (PKA) signaling through a CD36-dependent mechanism. Prostagla... Read More about Thrombospondin-1 induces platelet activation through CD36-dependent inhibition of the cAMP/protein kinase A signaling cascade.

Nitric oxide inhibits von Willebrand factor-mediated platelet adhesion and spreading through regulation of integrin α IIbβ 3 and myosin light chain (2009)
Journal Article
Roberts, W., Michno, A., Aburima, A., & Naseem, K. M. (2009). Nitric oxide inhibits von Willebrand factor-mediated platelet adhesion and spreading through regulation of integrin α IIbβ 3 and myosin light chain. Journal of thrombosis and haemostasis : JTH, 7(12), 2106-2115. https://doi.org/10.1111/j.1538-7836.2009.03619.x

Background: von Willebrand factor (VWF)-mediated platelet adhesion and spreading at sites of vascular injury is a critical step in hemostasis. This process requires two individual receptors: glycoprotein Ib (GPIb)-V-IX and integrin αIIbβ3. However, l... Read More about Nitric oxide inhibits von Willebrand factor-mediated platelet adhesion and spreading through regulation of integrin α IIbβ 3 and myosin light chain.

Globular adiponectin increases cGMP formation in blood platelets independently of nitric oxide (2008)
Journal Article
Riba, R., Patel, B., Aburima, A., & Naseem, K. M. (2008). Globular adiponectin increases cGMP formation in blood platelets independently of nitric oxide. Journal of thrombosis and haemostasis : JTH, 6(12), 2121-2131. https://doi.org/10.1111/j.1538-7836.2008.03179.x

Background: Platelet-derived nitric oxide (NO) has been shown to play conflicting roles in platelet function, although it is accepted that NO mediates its actions through soluble guanylyl cyclase (sGC). This confusion concerning the roles of platelet... Read More about Globular adiponectin increases cGMP formation in blood platelets independently of nitric oxide.