Chicoric acid prevents PDGF-BB-induced VSMC dedifferentiation, proliferation and migration by suppressing ROS/NFκB/mTOR/P70S6K signaling cascade

Abstract

Phenotypic switch of vascular smooth muscle cells (VSMCs) is characterized by increased expressions of VSMC synthetic markers and decreased levels of VSMC contractile markers, which is an important step for VSMC proliferation and migration during the development and progression of cardiovascular diseases including atherosclerosis. Chicoric acid (CA) is identified to exert powerful cardiovascular protective effects. However, little is known about the effects of CA on VSMC biology. Herein, in cultured VSMCs, we showed that pretreatment with CA dose-dependently suppressed platelet-derived growth factor type BB (PDGF-BB)-induced VSMC phenotypic alteration, proliferation and migration. Mechanistically, PDGF-BB-treated VSMCs exhibited higher mammalian target of rapamycin (mTOR) and P70S6K phosphorylation, which was attenuated by CA pretreatment, diphenyleneiodonium chloride (DPI), reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine (NAC) and nuclear factor-κB (NFκB) inhibitor Bay117082. PDGF-BB-triggered ROS production and p65-NFκB activation were inhibited by CA. In addition, both NAC and DPI abolished PDGF-BB-evoked p65-NFκB nuclear translocation, phosphorylation and degradation of Inhibitor κBα (IκBα). Of note, blockade of ROS/NFκB/mTOR/P70S6K signaling cascade prevented PDGF-BB-evoked VSMC phenotypic transformation, proliferation and migration. CA treatment prevented intimal hyperplasia and vascular remodeling in rat models of carotid artery ligation in vivo. These results suggest that CA impedes PDGF-BB-induced VSMC phenotypic switching, proliferation, migration and neointima formation via inhibition of ROS/NFκB/mTOR/P70S6K signaling cascade.

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“…Precious studies showed that ROS generation was associated with the proliferation of cancer cells. [18][19][20] To determine whether KRT17 affects ROS activation, we used DCFH-DA to detect intracellular ROS. As shown in Figure 4, after transfection with siKRT17 for 1 and 24 h, ROS activation increased over time.…”

MicroRNA‑24 attenuates diabetic vascular remodeling by�suppressing the NLRP3/caspase‑1/IL‑1β signaling pathway

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AKT/FOXO1 axis links cross-talking of endothelial cell and pericyte in TIE2-mutated venous malformations

“…Normal, mature and stable SMCs contain abundant muscle bers, with poor proliferation and migration ability, which are contractile phenotype. In response to vascular injury, the activated in ammatory cells, platelets and SMCs release the growth factors, especially platelet-derived growth factor (PDGF), thereby leading to a switch of SMCs from a contractile phenotype to a synthetic phenotype [48][49][50]. PDGFB is described to be one of the most potent stimulants for SMCs proliferation and migration [51].…”