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...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.展开更多
基金Priority Union Foundation of Yunnan Provincial Science and Technology Department and Kunming Medical University(202101AC070461).
文摘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.
