학술논문
Extracellular Vesicle Size Reveals Cargo Specific to Coagulation and Inflammation in Pediatric and Adult Sickle Cell Disease
Document Type
article
Author
Kiruphagaran Thangaraju PhD; Saini Setua PhD; Christina Lisk PhD; Delaney Swindle MS; Daniel Stephenson PhD; Monika Dzieciatkowska PhD; Derek R. Lamb BS; Parikshit Moitra PhD; David Pak MS; Kathryn Hassell MD; Gemlyn George MD; Rachelle Nuss MD; Pavel Davizon-Castillo MD; Kurt R. Stenmark MD; Angelo D’Alessandro PhD; David C. Irwin PhD; Paul W. Buehler PharmD, PhD
Source
Clinical and Applied Thrombosis/Hemostasis, Vol 29 (2023)
Subject
Language
English
ISSN
1938-2723
10760296
10760296
Abstract
Aberrant coagulation in sickle cell disease (SCD) is linked to extracellular vesicle (EV) exposure. However, there is no consensus on the contributions of small EVs (SEVs) and large EVs (LEVs) toward underlying coagulopathy or on their molecular cargo. The present observational study compared the thrombin potential of SEVs and LEVs isolated from the plasma of stable pediatric and adult SCD patients. Further, EV lipid and protein contents were analyzed to define markers consistent with activation of thrombin and markers of underlying coagulopathy. Results suggested that LEVs—but not SEVs—from pediatrics and adults similarly enhanced phosphatidylserine (PS)-dependent thrombin generation, and cell membrane procoagulant PS (18:0;20:4 and 18:0;18:1) were the most abundant lipids found in LEVs. Further, LEVs showed activated coagulation in protein pathway analyses, while SEVs demonstrated high levels of cholesterol esters and a protein pathway analysis that identified complement factors and inflammation. We suggest that thrombin potential of EVs from both stable pediatric and adult SCD patients is similarly dependent on size and show lipid and protein contents that identify underlying markers of coagulation and inflammation.