l-Palmitoylcarnitine potentiates plasmin and tPA to inhibit thrombosis

doi:10.1007/s13659-023-00413-z

应用天然产物 ›› 2023, Vol. 13 ›› Issue (6): 48-48.DOI: 10.1007/s13659-023-00413-z

• ORIGINAL ARTICLES • 上一篇下一篇

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

收稿日期:2023-09-18 出版日期:2023-12-24 发布日期:2023-12-26
通讯作者: Jianlin Shao,E-mail:shaojl@ydyy.cn;Zilei Duan,E-mail:duanzileikiz@126.com
基金资助:
This work was supported by Priority Union Foundation of Yunnan Provincial Science and Technology Department and Kunming Medical University (202101AC070461).

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

Received:2023-09-18 Online:2023-12-24 Published:2023-12-26
Contact: Jianlin Shao,E-mail:shaojl@ydyy.cn;Zilei Duan,E-mail:duanzileikiz@126.com
Supported by:
This work was supported by Priority Union Foundation of Yunnan Provincial Science and Technology Department and Kunming Medical University (202101AC070461).

摘要/Abstract

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 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.

关键词: l-palmitoylcarnitine, Coagulation, Plasmin, Tissue-type plasminogen activator, Thrombosis

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.

Key words: l-palmitoylcarnitine, Coagulation, Plasmin, Tissue-type plasminogen activator, Thrombosis

Juan Yang, Lina Cha, Yepeng Wang, Quan Zhang, Xiaopeng Tang, Jianlin Shao, Zilei Duan. l-Palmitoylcarnitine potentiates plasmin and tPA to inhibit thrombosis[J]. 应用天然产物, 2023, 13(6): 48-48.

Juan Yang, Lina Cha, Yepeng Wang, Quan Zhang, Xiaopeng Tang, Jianlin Shao, Zilei Duan. l-Palmitoylcarnitine potentiates plasmin and tPA to inhibit thrombosis[J]. Natural Products and Bioprospecting, 2023, 13(6): 48-48.

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l-Palmitoylcarnitine potentiates plasmin and tPA to inhibit thrombosis

l-Palmitoylcarnitine potentiates plasmin and tPA to inhibit thrombosis

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