Journal
VASCULAR PHARMACOLOGY
Volume 70, Issue -, Pages 23-34Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.vph.2015.03.002
Keywords
Myricitrin; Atherosclerosis; Oxidized low-density lipoprotein; Reactive oxygen species; Endothelial cells
Categories
Funding
- National Natural Science Foundation of China [81374011]
- Major Scientific and Technological Special Project for 'Significant New Drugs Formulation' [2012ZX09103201-004, 2012ZX09501001-004]
- Basic Scientific Research Projects of The Central Public Research Institutes [yz-12-11]
- Innovation Fund of Peking Union Medical College [2013-1007-04]
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Blood vessel endothelial dysfunction induced by oxidized low-density lipoprotein (ox-LDL) has been implicated in the pathogenesis of atherosclerosis and vasculopathy. The ox-LDL-elicited reactive oxygen species (ROS) release has been assumed to serve a critical function in endothelial damage. Myricitrin (from Myrica cerifera) is a natural antioxidant that has strong anti-oxidative, anti-inflammatory, and anti-nociceptive activities. However, the protective effect of myricitrin on ROS-induced endothelial cell injury and its related molecular mechanisms have never been investigated. This study demonstrates that myricitrin can inhibit ox-LDL-induced endothelial apoptosis and prevent plague formation at an early stage in an atherosclerotic mouse model. The administration of myricitrin in vivo decreases the thickness of the vascular wall in the aortic arch of ApoE -/- mice. In vitro study shows that ox-LDL-induced human umbilical vein endothelial cell apoptosis can be reduced upon receiving myricitrin pre-treatment. Treatment with myricitrin significantly attenuated ox-LDL-induced endothelial cell apoptosis by inhibiting LOX-1 expression and by increasing the activation of the STAT3 and PI3K/Akt/eNOS signaling pathways. At the same time, our result demonstrates that myricitrin treatment optimizes the balance of pro/anti-apoptosis proteins, including Bax, Bad, XIAP, cIAP-2, and survivin. Our study suggests that myricitrin treatment can effectively protect cells from ox-LDL-induced endothelial cell apoptosis, which results in reduced atherosclerotic plague formation. This result indicates that myricitrin can be used as a drug candidate for the treatment of cardiovascular diseases. (C) 2015 Published by Elsevier Inc.
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