Comparative analysis of Lox-1 and CD36 expression in human platelets and on circulating microparticles during ARDS-induced coagulopathy.
Pubmed ID: 39546984
Journal: Thrombosis research
Publication Date: Dec. 1, 2024
MeSH Terms: Humans, Male, Adult, Female, Middle Aged, Blood Platelets, Blood Coagulation Disorders, Lipoproteins, LDL, Respiratory Distress Syndrome, CD36 Antigens, Scavenger Receptors, Class E, Cell-Derived Microparticles
Authors: Leonard J, Kepplinger D, Torres E, Hu CH, Veneziano R, Hoemann CD
Cite As: Leonard J, Kepplinger D, Torres E, Hu CH, Veneziano R, Hoemann CD. Comparative analysis of Lox-1 and CD36 expression in human platelets and on circulating microparticles during ARDS-induced coagulopathy. Thromb Res 2024 Dec;244:109202. Epub 2024 Oct 31.
Studies:
- Acute Respiratory Distress Network (ARDSNet) Studies 06 and 08 Prospective, Randomized, Multicenter Trial of Aerosolized Albuterol Versus Placebo for the Treatment of Acute Lung Injury (ALTA)
- Acute Respiratory Distress Network (ARDSNet) Studies 07 and 08 Prospective, Randomized, Blinded, Placebo-controlled, Multi-center Trial of Omega-3 Fatty Acid, Gamma-Linolenic Acid, and Anti-Oxidant Supplementation in the Management of Acute Lung Injury or Acute Respiratory Distress Syndrome (Omega)
- Acute Respiratory Distress Network (ARDSNet) Studies 07, 08, 09, 11, and 12 Early Versus Delayed Enteral Feeding to Treat People with Acute Lung Injury or Acute Respiratory Distress Syndrome (EDEN)
Abstract
INTRODUCTION: Acute respiratory distress syndrome (ARDS) patients are at risk of thrombosis through mechanisms implicating oxidized low-density lipoprotein (oxLDL). Endothelial cells, immune cells and platelets were reported to express scavenger receptors for oxLDL: Lox-1 and CD36. We hypothesized that platelets shed a soluble Lox-1 ectodomain (sLox-1) and release CD36-bearing procoagulant microparticles (MPs), that both become elevated in subjects with ARDS-induced coagulopathy. METHODS: Using anti-extracellular and anti-intracellular Lox-1 antibodies, we first tested by western blot whether platelets express Lox-1 and shed sLox-1 upon activation. Next, we measured sLox-1 in blood plasma of 23 healthy donors and 48 ARDS Omega patients with and without coagulopathy, and assessed the corresponding MP fraction for Lox-1/sLox-1 and CD36. We evaluated mechanisms of sLox-1-MP association. Recombinant proteins were used as controls. RESULTS: Resting platelets expressed abundant CD36 (7.8 ng/μg protein extract) which was released upon oxLDL stimulation, but undetectable levels of full-length 37 kDa Lox-1 receptor or 24 kDa sLox-1 (below 10 pg/μg). In an RNAseq meta-analysis, platelets expressed negligible OLR1, the mRNA encoding Lox-1, compared to CD36. A subset of ARDS patients showed elevated plasma sLox-1 and MP-associated sLox-1 compared to healthy controls that was positively associated with 90-day survival and low coagulopathy. MP-associated CD36 was reduced in ARDS plasma compared to healthy donors and did not correlate with survival, coagulopathy, or sLox-1. oxLDL promoted sLox-1 binding to CD36-deficient MPs. CONCLUSION: sLox-1 arising from a non-platelet cell source associates with circulating MPs which could serve a protective role in ARDS.