2. Academic Validation
  3. L-Palmitoylcarnitine potentiates plasmin and tPA to inhibit thrombosis

L-Palmitoylcarnitine potentiates plasmin and tPA to inhibit thrombosis

  • Nat Prod Bioprospect. 2023 Nov 8;13(1):48. doi: 10.1007/s13659-023-00413-z.
Juan Yang # 1,  Lina Cha # 2,  Yepeng Wang # 3,  Quan Zhang 4,  Xiaopeng Tang 5,  Jianlin Shao 6,  Zilei Duan 7
Affiliations

Affiliations

  • 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.
  • 6 Department of Anesthesiology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China. shaojl@ydyy.cn.
  • 7 Small Molecule Drugs Sichuan Key Laboratory, Institute of Materia Medica, School of Pharmacy, Chengdu Medical College, Chengdu, 610500, China. duanzileikiz@126.com.
  • # Contributed equally.
PMID: 37938456 DOI: 10.1007/s13659-023-00413-z
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.

Keywords

Coagulation; L-palmitoylcarnitine; Plasmin; Thrombosis; Tissue-type plasminogen activator.

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