RT Journal Article
SR Electronic
T1 Plasma non-esterified fatty acids contribute to increased coagulability in type-2 diabetes through altered plasma zinc speciation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 744482
DO 10.1101/744482
A1 Amélie I. S. Sobczak
A1 Kondwani G. H. Katundu
A1 Fladia A. Phoenix
A1 Siavash Khazaipoul
A1 Ruitao Yu
A1 Fanuel Lampiao
A1 Fiona Stefanowicz
A1 Claudia A. Blindauer
A1 Samantha J. Pitt
A1 Terry K. Smith
A1 Ramzi A. Ajjan
A1 Alan J. Stewart
YR 2020
UL http://biorxiv.org/content/early/2020/07/27/744482.abstract
AB Zn2+ is an essential regulator of coagulation and its availability in plasma is fine-tuned through buffering by human serum albumin (HSA). Non-esterified fatty acids (NEFAs) transported by HSA reduce its ability to bind/buffer Zn2+. This is important as plasma NEFA levels are elevated in type-2 diabetes mellitus (T2DM) and other diseases with an increased risk of developing thrombotic complications. The presence of 5 mol. eq. of myristate, palmitate, stearate, palmitoleate and palmitelaidate reduced Zn2+ binding to HSA. Addition of myristate and Zn2+ increased thrombin-induced platelet aggregation in platelet-rich plasma and increased fibrin clot density and clot time in a purified protein system. The concentrations of key saturated (myristate, palmitate, stearate) and monounsaturated (oleate, vaccinate) NEFAs positively correlated with clot density in subjects with T2DM (and controls). Collectively, these data strongly support the concept that elevated NEFA levels contribute to an increased thrombotic risk in T2DM through dysregulation of plasma zinc speciation.Competing Interest StatementThe authors have declared no competing interest.