Key result
Oxidised HDL inhibits SFLLRN-stimulated platelet activation up to ~70%, while post-RIPC HDL shows no effect.
Why the study?
Oxidation of HDL enhances its ability to inhibit platelet activation, and remote ischaemic preconditioning (RIPC) causes mild increases in oxidative factors while inhibiting platelet activation. Whether RIPC inhibits platelet activation via oxidation of HDL was unknown.
Does remote ischaemic preconditioning inhibit platelet activation via oxidation of high-density lipoprotein in patients undergoing upper limb RIPC compared to in vitro copper sulphate-oxidised HDL?
Does remote ischaemic preconditioning inhibit platelet activation via oxidation of high-density lipoprotein in patients undergoing upper limb RIPC compared to in vitro copper sulphate-oxidised HDL?
Although remote ischaemic preconditioning inhibits ex vivo platelet activation, this effect is not mediated by oxidative modification of HDL and does not replicate the anti-platelet effects of in vitro oxidised HDL.
Answers are grounded in this paper and cite their sources.
OxHDL inhibits agonist-induced platelet activation markers in vitro; leaves open whether this mediates RIPC effects in vivo.
Background: High density lipoprotein (HDL) is associated with reduced thrombotic risk and can directly inhibit platelet activation.Oxidation of HDL has been demonstrated to enhance its ability to inhibit platelet activation.Remote ischaemic preconditioning (RIPC), which causes mild, cardioprotective increases in oxidative factors, inhibits platelet activation.Objectives: We therefore hypothesised that RIPC inhibited platelet activation via oxidation of HDL.Methods: We isolated HDL from the plasma of 12 patients before and after exposure to three cycles of upper limb RIPC, after which decreased platelet activation in response to the PAR1 agonist SFLLRN had been observed, and compared this to HDL isolated from healthy controls that was oxidised by copper sulphate in vitro (OxHDL).HDL was tested for its effect on platelet responsiveness to adenosine diphosphate (ADP), collagen-related peptide (CRP-XL), SFLLRN and PAR4 agonist AYPGFK.Results: Preincubation of washed platelets with OxHDL inhibited agonist-induced platelet expression of CD62P (e.g.reduces SFLLRN stimulation by 31%), CD63 (e.g.reduces SFLLRN stimulation by 52%) and conformational change of αIIbβ3 (e.g.reduces SFLLRN stimulation by 70%) and increased phosphorylation of vasodilator-stimulated phosphoprotein (VASP).In contrast there was no effect of pre-incubation with patient preRIPC-HDL or postRIPC-HDL, and postRIPC-HDL did not demonstrate the changes to apoA-I structure or HNE-adduct formation seen after copper sulphate exposure.Conclusions: We conclude that although RIPC inhibits ex vivo platelet activation, it does not do so via modification of HDL and does not replicate the biochemical or functional consequences of HDL oxidation.
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Reddel et al. (2026) studied Platelet activation (n=12). Remote ischaemic preconditioning (RIPC)-derived HDL vs. In vitro copper sulphate-oxidised HDL (OxHDL) from healthy controls and pre-RIPC HDL was evaluated on Agonist-induced platelet activation (CD62P expression, CD63 expression, and αIIbβ3 conformational change in response to SFLLRN). In vitro oxidised HDL reduced SFLLRN-stimulated platelet CD62P (by 31%), CD63 (by 52%), and αIIbβ3 activation (by 70%), whereas post-RIPC HDL had no effect.
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