Mildly oxidized HDL decrease agonist-induced platelet aggregation and release of pro-coagulant platelet extracellular

M Tafelmeier1, A Fischer1, E Orsó1

  • 1Institute for Clinical Chemistry and Laboratory Medicine, University Clinic of Regensburg Franz-Josef-Strauss-Allee 11, D-93052 Regensburg, Germany.

Insights

Mildly oxidized HDL (moxHDL) can improve platelet concentrate (PLC) quality by reducing platelet extracellular vesicle (PL-EV) release and enhancing platelet lipid homeostasis, potentially prolonging storage viability.

Area of Science:

  • Biochemistry
  • Hematology
  • Lipidomics

Background:

  • Stored platelet concentrates (PLCs) develop platelet storage lesion (PSL), impairing platelet (PLT) viability and function.
  • Oxidized high-density lipoprotein (oxHDL) effects on PLTs are poorly understood, unlike oxidized low-density lipoprotein (oxLDL).

Purpose of the Study:

  • To investigate the impact of native HDL (nHDL) and mildly oxidized HDL (moxHDL) on PLCs during storage.
  • To analyze the effects of moxHDL on platelet extracellular vesicle (PL-EV) release, aggregation, and lipid profiles.

Main Methods:

  • PLCs were treated with nHDL or moxHDL under blood banking conditions for 5 days.
  • Analyses included flow cytometry, nanoparticle tracking analysis (NTA), aggregometry, immunoblotting, and mass spectrometry.
  • Evaluated PL-EV release, PLT aggregation, protein expression, and lipid composition.

Main Results:

  • MoxHDL significantly decreased PL-EV release by 36% and partially reversed agonist-induced PLT aggregation compared to nHDL.
  • MoxHDL improved PLT membrane lipid homeostasis via enhanced lysophospholipid uptake and remodeling, increasing the sphingomyelin/ceramide ratio.
  • CD36 and scavenger receptor-B1 (SR-B1) protein content increased in secreted PL-EVs.

Conclusions:

  • MoxHDL improves PLT membrane lipid homeostasis and antagonizes PL-EV release and aggregation in stored PLCs.
  • This effect is likely due to enhanced lipid remodeling mediated by CD36 and SR-B1.
  • MoxHDL shows potential as an in vitro supplement to improve PLC quality and extend storage duration.

Related Concept Videos

Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors01:20

Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors

Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
1.5K
Formation of the Platelet Plug01:22

Formation of the Platelet Plug

The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
10.5K
Anticoagulant Drugs: Low-Molecular-Weight Heparins01:30

Anticoagulant Drugs: Low-Molecular-Weight Heparins

Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
2.3K
Coronary Artery Disease II: Pathophysiology01:26

Coronary Artery Disease II: Pathophysiology

Coronary Artery Disease (CAD) originates from a series of events that impair the function of coronary arteries, the blood vessels responsible for delivering oxygen-rich blood to the heart muscle. The pathophysiology of CAD is closely linked to atherosclerosis, a chronic inflammatory and lipid-driven condition affecting the vascular endothelium.1. Endothelial DamageThe process begins with damage to the vascular endothelium, which serves as a protective barrier between the blood and the vessel...
937
Atherosclerosis III: Management01:26

Atherosclerosis III: Management

Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
571
Oxidation of Phenols to Quinones01:17

Oxidation of Phenols to Quinones

In the presence of oxidizing agents, phenols are oxidized to quinones. Quinones can be easily reduced back to phenols using mild reducing agents. The electron-donating hydroxyl group enhances the reactivity of the aromatic ring, enabling oxidation of the ring even in the absence of an α hydrogen.
o-hydroxy phenols are oxidized to o-quinones and p-hydroxy phenols to p-quinones. Such redox reactions involve the transfer of two electrons and two protons. The reversible redox...
5.2K