Serum Levels of IL‐1β, IL‐6, TGF‐β, and MMP‐9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP‐9 in a New In Vitro Model of THP‐1 Cells Activated by Stenting

Abstract

Inflammation plays an important role in the pathophysiological process after carotid artery stenting (CAS). Monocyte is a significant source of inflammatory cytokines in vascular remodeling. Telmisartan could reduce inflammation. In our study, we first found that, after CAS, the serum IL-1β, IL-6, TGF-β, and MMP-9 levels were significantly increased, but only MMP-9 level was elevated no less than 3 months. Second, we established a new in vitro model, where THP-1 monocytes were treated with the supernatants of human umbilical vein endothelial cells (HUVECs) that were scratched by pipette tips, which mimics monocytes activated by mechanical injury of stenting. The treatment enhanced THP-1 cell adhesion, migration and invasion ability, and the phosphorylation of ERK1/2 and Elk-1 and MMP-9 expression were significantly increased. THP-1 cells pretreated with PD98095 (ERK1/2 inhibitor) attenuated the phosphorylation of ERK1/2 and Elk-1 and upregulation of MMP-9, while pretreatment with telmisartan merely decreased the phosphorylation of Elk-1 and MMP-9 expression. These results suggested that IL-1β, IL-6, TGF-β, and MMP-9 participate in the pathophysiological process after CAS. Our new in vitro model mimics monocytes activated by stenting. MMP-9 expression could be regulated through ERK1/2/Elk-1 pathway, and the protective effects of telmisartan after stenting are partly attributed to its MMP-9 inhibition effects via suppression of Elk-1.

High fat diet induced atherosclerosis is accompanied with low colonic bacterial diversity and altered abundances that correlates with plaque size, plasma A-FABP and cholesterol: a pilot study of high fat diet and its intervention with Lactobacillus rhamnosus GG (LGG) or telmisartan in ApoE−/− mice

“…The inhibitory effects of TLM on A-FABP [64, 65] and monocytic cell adhesions [66] may have been mediated by PPARƔ activation; and on MMP-9 [67–72] by Elk-1 phosphorylation inhibition [67]. While TLM was previously shown to lower cholesterol [73, 74], possibly through inhibiting intestinal cholesterol absorption [74], such reduction was not seen in the current study.…”

Sanhuang Xiexin decoction promotes good functional outcome in acute ischemic stroke

“…The treatment of acute ischemic stroke (AIS) is a very complicated process, but the effect of Western medicine treatment is not satisfactory (Xu & Li, 2011). It has been proven that the traditional Chinese medicine can play the advantage of treating both root causes and symptoms of inflammatory response in AIS patients with endovascular intervention examination (Zhang et al, 2015). It has been proven that the traditional Chinese medicine can play the advantage of treating both root causes and symptoms of inflammatory response in AIS patients with endovascular intervention examination (Zhang et al, 2015).…”

“…The traditional Chinese medicine has been used in vascular disease treatment for thousands of years in the Asia-Pacific region. It has been proven that the traditional Chinese medicine can play the advantage of treating both root causes and symptoms of inflammatory response in AIS patients with endovascular intervention examination (Zhang et al, 2015).…”

MMP-9 and/or TIMP as predictors of ischaemic stroke in patients with symptomatic and asymptomatic atherosclerotic stenosis of carotid artery treated by stenting or endarterectomy – A review

“…Concentrations of MMP-9 and/or TIMP in CS patients subjected to stenting (CAS) or endarterectomy (CEA) Zhang et al conducted an extensive study to verify an association between serum level of MMP-9 and the stenting procedure. In this study, concentrations of MMP-9 were assessed prior to the procedure, 24 h, 3-and 6-month thereafter [16]. Elevated levels of MMP-9 were observed for at least 3 months post-procedure, which suggested that this metalloproteinase may be involved in the process of in-stent stenosis.…”

“…Analyse of MMP-9 level in patients with symptomatic CS treated by stenting (n = 57) showed elevated levels of MMP-9 not only 24 h post-stenting but also up to 30 days thereafter; concentrations of MMP-9 determined prior to the stenting, 24 h and 30 days post-procedure amounted to 100 pg/ml, 125 pg/ml and 118 pg/ml, respectively (Setacci et al similar to Zhang et al). Carotid stenting was associated with two TIA episodes directly after the procedure, two TIA episode and death within a month after the discharge from the hospital [16,17].…”