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. 2022 Aug 16;23(16):9199. doi: 10.3390/ijms23169199

Figure 1.

Figure 1

Major signalling events downstream platelet scavenger receptors induced by oxidatively modified LDL. Platelets are exposed to different types of oxidatively modified LDL, which interact with distinct pattern recognition receptors on their surface. Given that these particles have a complex and varied chemical composition, there is potential for particular LDL species to interact with different receptors. OxLDL has been shown to interact with CD36, SRA1, and potentially LOX-1. In contrast, electronegative LDL (fraction L5) has currently only been shown to interact with LOX-1. TLR2 has not been shown to bind with oxLDL but does interact with specific oxidised phospholipids that are known to be present in oxLDL (oxPCCD36). LOX-1 is located in the alpha granules of resting platelets and recruited to the platelet surface upon platelet activation. Once at the platelet surface, LOX-1 can bind electronegative LDL to stimulate signalling events (yellow) through PI3K and JNK to increase P-selectin expression and integrin aIIbb3 activation. SR-A1 binds oxLDL to initiate signalling through JNK and p38 (red), which can drive P-selectin expression, aIIbb3 activation, shape change, and TxA2. CD36 is constitutively associated with the Src family kinases Fyn and Lyn and, once ligated by oxLDL, incites a multitude of pathways (Blue). These drive shape change through RhoA and MLCP, P-selectin expression, and aIIbb3 activation through Vav1/3 and PLCg2. This pathway also leads to the activation of a PKC isoform, which is critical to the control of membrane phospholipids and inhibitory signalling (green). PKC induces the ROS generation through NOX2, which activates both ERK and phosphatidyl serine exposure, as well as the inhibition of PKG. PKC also activates PDE3A, which reduces cAMP concentrations and the activation of PKA. TLR2 does not bind oxLDL, but interaction with oxidised phospholipids leads to the MyD88-mediated activation of tyrosine kinase signalling, P-selectin expression, and aIIbb3 activation. Abbreviations: Phosphoinositide 3-kinase (PI3K), c-Jun N-terminal kinase (JNK), Myosin light chain phosphatase (MLCP), extracellular-signal regulated kinases (ERK), Protein kinase G (PKG), Protein kinase A (PKA), Protein kinase C (PKC), Phospholipase C gamma 2 (PLCg2), Vav1/3, NADPH Oxidase 2 (NOX2), p38.