L-Palmitoylcarnitine potentiates plasmin and tPA to inhibit thrombosis.

Nat Prod Bioprospect

Small Molecule Drugs Sichuan Key Laboratory, Institute of Materia Medica, School of Pharmacy, Chengdu Medical College, Chengdu, 610500, China.

Published: November 2023

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 the β-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 and 4.46 × 10 M, respectively, showing high affinities. In mouse model, L-PC administration significantly inhibited FeCl-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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10632336PMC
http://dx.doi.org/10.1007/s13659-023-00413-zDOI Listing

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