Piperine Inhibits Platelet-Derived Growth Factor-BB-Induced Proliferation and Migration in Vascular Smooth Muscle Cells

Abstract

The proliferation and migration of vascular smooth muscle cells (VSMCs) in blood vessels are important in the pathogenesis of vascular disorders such as atherosclerosis and restenosis. Piperine, a major component of black pepper, has antioxidant, anticancer, and anti-inflammatory activity. However, the antiatherosclerotic effects of piperine have not been investigated. In this study, the effects of piperine on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs were investigated. The antiproliferative effects of piperine were determined using MTT assays, cell counting, real-time polymerase chain reaction, and western blots. Our results showed that piperine significantly attenuated the proliferation of VSMCs by increasing the expression of p27(kip1), regulating the mRNA expression of cell cycle enzymes (cyclin D, cyclin E, and PCNA), and decreasing the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in a noncytotoxic concentration-dependent manner (30-100 μM). Moreover, we examined the effects of piperine on the migration of PDGF-BB-stimulated VSMCs, as determined by the Boyden chamber assay, H2DCFDA staining, and western blots. Our results showed that 100 μM piperine decreased cell migration, the production of reactive oxygen species (ROS), and phosphorylation of the p38 mitogen-activated protein kinase (MAPK). Taken together, our results suggest that piperine inhibits PDGF-BB-induced proliferation and the migration of VSMCs by inducing cell cycle arrest and suppressing MAPK phosphorylation and ROS. These findings suggest that piperine may be beneficial for the treatment of vascular-related disorders and diseases.

Oxymatrine suppresses MOVAS proliferation induced by platelet-derived growth factor via G0/G1 arrest

“…PDGF, mainly expressed in VSMCs and endothelial cells, promote mitosis and play an important role in the proliferation of VSMCs [6][7][8]37]. The binding of PDGF-BB, a subtype of PDGF released from injured vessels, to its receptor can trigger the activation of downstream and then contribute significantly to VSMCs proliferation [9][10][11][12]. In this paper, PDGF-BB could effectively induce MOVAS proliferation, which was consistent with the previous studies reported.…”

“…Platelet-Derived Growth Factor (PDGF) is an important regulator that stimulates the proliferation of VSMCs [6][7][8]. The binding of PDGF-BB, a subtype of PDGF, to its receptor triggers the activation of downstream signaling molecules such as Mitogen-Activated Protein Kinases (MAPKs) to promote VSMCs proliferation and growth [9][10][11][12][13]. Therefore, preventing the PDGF-BB induced VSMCs proliferation might be a promising strategy for treating the development of neointima in atherosclerosis and post-angioplasty restenosis in the future.…”

The Role of Myeloid Cell-Derived PDGF-B in Neotissue Formation in a Tissue-Engineered Vascular Graft

“…Interestingly, our results did not demonstrate any differences in the area fraction of α-SMA + SMCs in 2-week specimens, but did identify decreased SMC proliferation in the PGDF-KO group. The decreased proliferation in PGDF-KO mice is consistent with literature demonstrating the paracrine role of PDGF in promoting SMC migration and proliferation [10,[22][23][24][25]. One potential reason that no difference was observed in the total quantity of SMCs between the two groups is that we specifically targeted only the PDGF-B subtype.…”

Piperine Congeners as Inhibitors of Vascular Smooth Muscle Cell Proliferation

“…The main constituent piperine is reported to enhance drug bioavailability and to modulate GABA A receptors, besides various other pharmacological activities, including analgesic, anti-inflammatory, anti-pyretic, anti-convulsive, anti-oxidant, anti-depressant, anti-apoptotic, anti-cancer, and anti-viral properties [12,[19][20][21]. In this study, we identified piperine (1) to be a promising inhibitor of VSMC proliferation, which was very recently also described by others [22]. We used piperine as lead compound to synthesize derivatives thereof and isolated structurally related amides from the fruits of P. nigrum to deduce a qualitative SAR with regard to the anti-proliferative effect in VSMCs.…”

“…All ). In addition to the isolated compounds, 15 further congeners were synthesized (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). All piperine analogues were subjected to cell-based assays.…”