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

• Authors: Dong Ju Son, Emory University; Soo Yeon Kim, Korea Basic Science Institute; Seong Su Han, University of Iowa; Chan Woo Kim, Emory University; Sandeep Kumar, Emory University; Byeoung Soo Park, Nanotoxtech Co., South Korea; Sung Eun Lee, Kyungpook National University; Yeo Pyo Yun, Chungbuk National University; Hanjoong Jo, Emory University; Young Hyun Park, Soonchunhyung University
• Journal Title: Biochemical and Biophysical Research Communications
• Volume: Volume 427, Number 2
• Publisher: Elsevier: 12 months | 2012-10-19, Pages 349-354
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.bbrc.2012.09.061
• Subjects: Engineering, Biomedical
• Keywords: Piperlongumine; atherosclerosis; vascular smooth muscle cells; PDGF receptor; NF-κB

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-κB) 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 C1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-κB—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.