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Title: Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling

Abstract

Highlights: Black-Right-Pointing-Pointer Anti-atherogenic effect of PL was examined using partial carotid ligation model in ApoE KO mice. Black-Right-Pointing-Pointer PL prevented atherosclerotic plaque development, VSMCs proliferation, and NF-{kappa}B activation. Black-Right-Pointing-Pointer Piperlongumine reduced vascular smooth muscle cell activation through PDGF-R{beta} and NF-{kappa}B-signaling. Black-Right-Pointing-Pointer PL may serve as a new therapeutic molecule for atherosclerosis treatment. -- Abstract: Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murine model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significantly reduced atherosclerotic plaque formation as well as proliferation and nuclear factor-kappa B (NF-{kappa}B) activation in an in vivo setting. PL treatment in VSMCs in vitro showed inhibition of migration and platelet-derived growth factor BB (PDGF-BB)-induced proliferation to the in vivo findings. We further identified that PL inhibited PDGF-BB-induced PDGF receptor beta activation and suppressed downstream signaling molecules such as phospholipase C{gamma}1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-{kappa}B-amore » downstream transcriptional regulator in PDGF receptor signaling, in response to PDGF-BB stimulation. In conclusion, our findings demonstrate a novel, therapeutic mechanism by which PL suppresses atherosclerosis plaque formation in vivo.« less

Authors:
 [1];  [2];  [3];  [4];  [1];  [2];  [5];  [1];  [2];  [6];  [7];  [8];  [1];  [2];  [5];  [9]
  1. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States)
  2. (United States)
  3. Division of Life Science, Korea Basic Science Institute, Daejeon (Korea, Republic of)
  4. University of Iowa Carver College of Medicine, Department of Pathology, Iowa City, IA (United States)
  5. (Korea, Republic of)
  6. Nanotoxtech Co., Ansan (Korea, Republic of)
  7. Division of Applied Biology and Chemistry, Kyungpook National University, Daegu (Korea, Republic of)
  8. College of Pharmacy, Chungbuk National University, Cheongju (Korea, Republic of)
  9. Department of Food Science and Nutrition, College of Natural Sciences, Soonchunhyang University, Asan (Korea, Republic of)
Publication Date:
OSTI Identifier:
22210295
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 427; Journal Issue: 2; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALKALOIDS; ARTERIOSCLEROSIS; CELL PROLIFERATION; GROWTH FACTORS; IN VITRO; IN VIVO; INFLAMMATION; INHIBITION; MICE; MUSCLES; PEPPERS; PHOSPHOTRANSFERASES; PLAQUE FORMATION; RECEPTORS

Citation Formats

Son, Dong Ju, Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, Kim, Soo Yeon, Han, Seong Su, Kim, Chan Woo, Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, Department of Bioinspired Science, Ehwa Womans University, Seoul, Kumar, Sandeep, Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, Park, Byeoung Soo, Lee, Sung Eun, Yun, Yeo Pyo, Jo, Hanjoong, E-mail: hjo@emory.edu, Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, Department of Bioinspired Science, Ehwa Womans University, Seoul, and Park, Young Hyun, E-mail: pyh012@sch.ac.kr. Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling. United States: N. p., 2012. Web. doi:10.1016/J.BBRC.2012.09.061.
Son, Dong Ju, Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, Kim, Soo Yeon, Han, Seong Su, Kim, Chan Woo, Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, Department of Bioinspired Science, Ehwa Womans University, Seoul, Kumar, Sandeep, Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, Park, Byeoung Soo, Lee, Sung Eun, Yun, Yeo Pyo, Jo, Hanjoong, E-mail: hjo@emory.edu, Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, Department of Bioinspired Science, Ehwa Womans University, Seoul, & Park, Young Hyun, E-mail: pyh012@sch.ac.kr. Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling. United States. doi:10.1016/J.BBRC.2012.09.061.
Son, Dong Ju, Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, Kim, Soo Yeon, Han, Seong Su, Kim, Chan Woo, Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, Department of Bioinspired Science, Ehwa Womans University, Seoul, Kumar, Sandeep, Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, Park, Byeoung Soo, Lee, Sung Eun, Yun, Yeo Pyo, Jo, Hanjoong, E-mail: hjo@emory.edu, Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, Department of Bioinspired Science, Ehwa Womans University, Seoul, and Park, Young Hyun, E-mail: pyh012@sch.ac.kr. Fri . "Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling". United States. doi:10.1016/J.BBRC.2012.09.061.
@article{osti_22210295,
title = {Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling},
author = {Son, Dong Ju and Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA and Kim, Soo Yeon and Han, Seong Su and Kim, Chan Woo and Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA and Department of Bioinspired Science, Ehwa Womans University, Seoul and Kumar, Sandeep and Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA and Park, Byeoung Soo and Lee, Sung Eun and Yun, Yeo Pyo and Jo, Hanjoong, E-mail: hjo@emory.edu and Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA and Department of Bioinspired Science, Ehwa Womans University, Seoul and Park, Young Hyun, E-mail: pyh012@sch.ac.kr},
abstractNote = {Highlights: Black-Right-Pointing-Pointer Anti-atherogenic effect of PL was examined using partial carotid ligation model in ApoE KO mice. Black-Right-Pointing-Pointer PL prevented atherosclerotic plaque development, VSMCs proliferation, and NF-{kappa}B activation. Black-Right-Pointing-Pointer Piperlongumine reduced vascular smooth muscle cell activation through PDGF-R{beta} and NF-{kappa}B-signaling. Black-Right-Pointing-Pointer PL may serve as a new therapeutic molecule for atherosclerosis treatment. -- Abstract: Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murine model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significantly reduced atherosclerotic plaque formation as well as proliferation and nuclear factor-kappa B (NF-{kappa}B) activation in an in vivo setting. PL treatment in VSMCs in vitro showed inhibition of migration and platelet-derived growth factor BB (PDGF-BB)-induced proliferation to the in vivo findings. We further identified that PL inhibited PDGF-BB-induced PDGF receptor beta activation and suppressed downstream signaling molecules such as phospholipase C{gamma}1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-{kappa}B-a downstream transcriptional regulator in PDGF receptor signaling, in response to PDGF-BB stimulation. In conclusion, our findings demonstrate a novel, therapeutic mechanism by which PL suppresses atherosclerosis plaque formation in vivo.},
doi = {10.1016/J.BBRC.2012.09.061},
journal = {Biochemical and Biophysical Research Communications},
number = 2,
volume = 427,
place = {United States},
year = {Fri Oct 19 00:00:00 EDT 2012},
month = {Fri Oct 19 00:00:00 EDT 2012}
}