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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Physiol. | doi: 10.3389/fphys.2019.01128

Cardiotonic pills plus recombinant human prourokinase ameliorates atherosclerotic lesions in LDLR-/- mice

 Jing-yan Han1, 2, 3, 4, 5, 6*, Jing-na Deng2, 4, 5, 6, 7, 8, Quan Li2, 4, 5, 6, 8, Kai Sun2, 3, 4, 5, 6, Chun-shui Pan2, 3, 4, 5, 6, Jing-yu Fan2, 3, 4, 5, 6, Bai-he Hu2, 3, 4, 5, 6, 9, Xin Chang2, 3, 4, 5, 6 and Huan Li2, 3, 4, 5, 6, 7
  • 1Integration of Chinese and Western Medicine, Peking University, China
  • 2Tasly Microcirculation Research Center, Peking University Health Science Center, China
  • 3State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica (IMM), China
  • 4Key laboratory of microcirculation, State Administration of Traditional Chinese Medicine of the People's Republic of China, China
  • 5Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China, China
  • 6State Key Laboratory of Core Technology in Innovative Chinese Medicine, China
  • 7Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, China
  • 8Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, China
  • 9Stake Key Laboratory of Core Technology in Innovative Chinese Medicine, China

Aim: This study was to explore the protective effects of cardiotonic pills (CP) or/and recombinant human prourokinase (proUK) on the atherosclerosis and the potential underlying mechanism.
Methods and Results: Atherosclerosis was induced in LDLR-/- mice by high fat diet contained 20% lard and 0.5% cholesterol. Daily oral administration of CP (130 mg/kg) or/and intravenous injection of proUK (2.5 mg/kg, twice a week) began at 8 weeks after feeding with high fat diet and continued for 4 weeks. CP alone treatment markedly decreased plasma triglyceride, but did not ameliorate atherosclerosis plaque. No effect was observed for proUK alone on any endpoints tested. CP plus proUK induced a significantly reduction in the atherosclerotic lesions, along with decreased levels of total cholesterol, triglyceride in the plasma. CP plus proUK inhibited the elevated hepatic total cholesterol and triglyceride in high fat diet-fed LDLR-/- mice, up-regulating the expressions of ATP-binding cassette gene 5 and 8, and adipose triglyceride lipase. In the aorta, CP plus proUK inhibited the expression of scavenger receptor A and CD36 in LDLR-/- mice. In addition, we observed that systemic inflammation was inhibited, manifested downregulation of plasma macrophage inflammatory protein-1α and intercellular cell adhesion molecule-1.
Conclusion: CP plus proUK effectively attenuated atherosclerosis plaque in LDLR-/- mice, which is associated with normalizing the lipid metabolism in the liver and aorta, reducing phagocytosis of receptor-mediated modified-LDL uptake and inhibiting systemic inflammation.

Keywords: Atherosclerosis, Inflammation, ATP-binding cassette gene 8, Adipose triglyceride lipase, Scavenger receptor A, CD36

Received: 14 Sep 2018; Accepted: 15 Aug 2019.

Copyright: © 2019 Han, Deng, Li, Sun, Pan, Fan, Hu, Chang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Jing-yan Han, Peking University, Integration of Chinese and Western Medicine, Beijing, 100191, China, hanjingyan@bjmu.edu.cn