Regulation of oxidized platelet lipidome: implications for coronary artery disease

Area of Science:

• Cardiovascular Biology
• Platelet Physiology
• Lipid Metabolism

Background:

• Hyperlipidaemia increases thrombosis risk, and oxidized LDL (oxLDL) binding to platelets in acute coronary syndrome (ACS) correlates with activation.
• Platelet lipid profiles in symptomatic coronary artery disease (CAD) patients are not well understood.

Purpose of the Study:

• To investigate the platelet lipidome in symptomatic CAD patients.
• To explore the functional consequences of the chemokine CXCL12 and its receptors CXCR-4/-7 on platelet lipid uptake.

Main Methods:

• Flow cytometry to detect platelet-oxLDL and CXCR4/7 expression.
• Liquid chromatography-high-resolution mass spectrometry for lipidomic analysis.
• Calibrated automated thrombinoscopy and live imaging microscopy to assess platelet function.
• In vivo mouse models of thrombosis.

Main Results:

• Platelet-oxLDL was elevated in CAD patients and correlated with CXCR7 and inversely with CXCR4 expression.
• Intracoronary thrombi in ACS patients showed oxLDL deposition in platelet-rich areas.
• LDL-oxLDL uptake increased oxidative stress, lipid peroxidation, and platelet activation (degranulation, integrin activation, apoptosis, thrombin generation).
• LDL-oxLDL enhanced thrombus formation in vitro and in vivo.
• CXCL12 modulated LDL-oxLDL uptake and augmented its pro-thrombotic effects.

Conclusions:

• An altered platelet lipidome is associated with thrombotic risk in CAD.
• The CXCL12-CXCR4-CXCR7 axis may be a key regulator of this mechanism in platelets.