Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling. 2012

Dong Ju Son, and Soo Yeon Kim, and Seong Su Han, and Chan Woo Kim, and Sandeep Kumar, and Byeoung Soo Park, and Sung Eun Lee, and Yeo Pyo Yun, and Hanjoong Jo, and Young Hyun Park
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30322, USA.

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 Cγ1, 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.

UI MeSH Term Description Entries
D008026 Ligation Application of a ligature to tie a vessel or strangulate a part. Ligature,Ligations,Ligatures
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D002339 Carotid Arteries Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. Arteries, Carotid,Artery, Carotid,Carotid Artery
D004148 Dioxolanes
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001057 Apolipoproteins E A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III. Apo-E,Apo E,Apo E Isoproteins,ApoE,Apolipoprotein E Isoproteins,Apoprotein (E),Apoproteins E,Isoproteins, Apo E,Isoproteins, Apolipoprotein E
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D016328 NF-kappa B Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA. Immunoglobulin Enhancer-Binding Protein,NF-kappa B Complex,Nuclear Factor kappa B,Transcription Factor NF-kB,kappa B Enhancer Binding Protein,Ig-EBP-1,NF-kB,NF-kappaB,Nuclear Factor-Kappab,Complex, NF-kappa B,Enhancer-Binding Protein, Immunoglobulin,Factor NF-kB, Transcription,Factor-Kappab, Nuclear,Ig EBP 1,Immunoglobulin Enhancer Binding Protein,NF kB,NF kappa B Complex,NF kappaB,NF-kB, Transcription Factor,Nuclear Factor Kappab,Transcription Factor NF kB

Related Publications

Dong Ju Son, and Soo Yeon Kim, and Seong Su Han, and Chan Woo Kim, and Sandeep Kumar, and Byeoung Soo Park, and Sung Eun Lee, and Yeo Pyo Yun, and Hanjoong Jo, and Young Hyun Park
January 2017, PloS one,
Dong Ju Son, and Soo Yeon Kim, and Seong Su Han, and Chan Woo Kim, and Sandeep Kumar, and Byeoung Soo Park, and Sung Eun Lee, and Yeo Pyo Yun, and Hanjoong Jo, and Young Hyun Park
January 2015, International journal of clinical and experimental medicine,
Dong Ju Son, and Soo Yeon Kim, and Seong Su Han, and Chan Woo Kim, and Sandeep Kumar, and Byeoung Soo Park, and Sung Eun Lee, and Yeo Pyo Yun, and Hanjoong Jo, and Young Hyun Park
December 1997, Kidney international,
Dong Ju Son, and Soo Yeon Kim, and Seong Su Han, and Chan Woo Kim, and Sandeep Kumar, and Byeoung Soo Park, and Sung Eun Lee, and Yeo Pyo Yun, and Hanjoong Jo, and Young Hyun Park
September 2013, Molecular nutrition & food research,
Dong Ju Son, and Soo Yeon Kim, and Seong Su Han, and Chan Woo Kim, and Sandeep Kumar, and Byeoung Soo Park, and Sung Eun Lee, and Yeo Pyo Yun, and Hanjoong Jo, and Young Hyun Park
November 2018, Molecular and cellular endocrinology,
Dong Ju Son, and Soo Yeon Kim, and Seong Su Han, and Chan Woo Kim, and Sandeep Kumar, and Byeoung Soo Park, and Sung Eun Lee, and Yeo Pyo Yun, and Hanjoong Jo, and Young Hyun Park
July 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie,
Dong Ju Son, and Soo Yeon Kim, and Seong Su Han, and Chan Woo Kim, and Sandeep Kumar, and Byeoung Soo Park, and Sung Eun Lee, and Yeo Pyo Yun, and Hanjoong Jo, and Young Hyun Park
January 2012, Vascular pharmacology,
Dong Ju Son, and Soo Yeon Kim, and Seong Su Han, and Chan Woo Kim, and Sandeep Kumar, and Byeoung Soo Park, and Sung Eun Lee, and Yeo Pyo Yun, and Hanjoong Jo, and Young Hyun Park
November 2015, IUBMB life,
Dong Ju Son, and Soo Yeon Kim, and Seong Su Han, and Chan Woo Kim, and Sandeep Kumar, and Byeoung Soo Park, and Sung Eun Lee, and Yeo Pyo Yun, and Hanjoong Jo, and Young Hyun Park
January 2017, American journal of translational research,
Dong Ju Son, and Soo Yeon Kim, and Seong Su Han, and Chan Woo Kim, and Sandeep Kumar, and Byeoung Soo Park, and Sung Eun Lee, and Yeo Pyo Yun, and Hanjoong Jo, and Young Hyun Park
June 1993, Nihon rinsho. Japanese journal of clinical medicine,
Copied contents to your clipboard!