| ORIGINAL ARTICLES |
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l-Palmitoylcarnitine potentiates plasmin and tPA to inhibit thrombosis |
| Juan Yang1, Lina Cha2, Yepeng Wang3, Quan Zhang4, Xiaopeng Tang5, Jianlin Shao1, Zilei Duan4 |
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 |
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Abstract 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 6.47×10–9 and 4.46×10–9 M, respectively, showing high affinities. In mouse model, L-PC administration significantly inhibited FeCl3-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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| Keywords
l-palmitoylcarnitine
Coagulation
Plasmin
Tissue-type plasminogen activator
Thrombosis
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| Fund:This work was supported by Priority Union Foundation of Yunnan Provincial Science and Technology Department and Kunming Medical University (202101AC070461). |
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Corresponding Authors:
Jianlin Shao,E-mail:shaojl@ydyy.cn;Zilei Duan,E-mail:duanzileikiz@126.com
E-mail: shaojl@ydyy.cn;duanzileikiz@126.com
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Issue Date: 26 December 2023
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