L-Palmitoylcarnitine potentiates plasmin and tPA to inhibit thrombosis  

作　　者：Juan Yang Lina Cha Yepeng Wang Quan Zhang Xiaopeng Tang Jianlin Shao Zilei Duan 

机构地区：[1]Department of Anesthesiology,First Affiliated Hospital of Kunming Medical University,Kunming 650032,China [2]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China [3]College of Life Sciences,Nanjing Agricultural University,Nanjing 210095,China [4]Small Molecule Drugs Sichuan Key Laboratory,Institute of Materia Medica,School of Pharmacy,Chengdu Medical College,Chengdu 610500,China [5]School of Basic Medicine,Qingdao University,Qingdao 266071,Shandong,China

出　　处：《Natural Products and Bioprospecting》2023年第1期171-180,共10页应用天然产物（英文）

基　　金：Priority Union Foundation of Yunnan Provincial Science and Technology Department and Kunming Medical University(202101AC070461).

摘　　要：L-Palmitoylcarnitine(L-PC)is an important endogenous fatty acid metabolite.Its classical biological functions are involved in the regulations of membrane molecular dynamics and theβ-oxidation of fatty acids.Decreased plasma long-chain acylcarnitines showed the association of venous thrombosis,implying anticoagulant activity of the metabolites and inspiring us to investigate if and how L-PC,a long-chain acylcarnitine,takes part in coagulation.Here we show that L-PC exerted anti-coagulant effects by potentiating the enzymatic activities of plasmin and tissue plasminogen activator(tPA).L-PC directly interacts with plasmin and tPA with an equilibrium dissociation constant(KD)of 6.47×10^(-9)and 4.46×10^(-9)M,respectively,showing high affinities.In mouse model,L-PC administration significantly inhibited FeCl_(3)-induced arterial thrombosis.It also mitigated intracerebral thrombosis and inflammation in a transient middle cerebral artery occlusion(tMCAO)mouse model.L-PC induced little bleeding complications.The results show that L-PC has anti-thrombotic function by potentiating plasmin and tPA.

关 键 词：L-palmitoylcarnitine COAGULATION PLASMIN Tissue-type plasminogen activator THROMBOSIS 

分 类 号：O6[理学—化学]