Dataset Information

Crosstalk between TGF-?/Smad3 and BMP/BMPR2 signaling pathways via miR-17-92 cluster in carotid artery restenosis.

ABSTRACT: In the recent decades, carotid angioplasty and stenting (CAS) has been developed into a credible option for the patients with carotid stenosis. However, restenosis remains a severe and unsolved issue after CAS treatment. Restenosis is characterized by neointimal hyperplasia, which is partially caused by vascular smooth muscle cells (VSMC) proliferation. However, the molecular mechanism involved in the restenosis is still unclear. In this study, we demonstrated a functional crosstalk between two TGF-? superfamily signaling pathway members, Smad3 and BMPR2, in VSMC proliferation. Smad3 plays an important role in the TGF-?/Smad3 signaling pathway, and is significantly upregulated in the carotid artery with restenosis to promote VSMC proliferation. In contrast, BMP receptor II (BMPR2), an inhibitor of VSMC proliferation is downregulated in carotid restenosis. We further found that BMPR2 downregulation is mediated by miR-17-92 cluster, which is transcriptionally regulated by Smad3. Thus, Smad3 upregulation and Smad3/miR-17-92 cluster-dependent BMPR2 downregulation are likely to promote VSMC proliferation and restenosis. Taken together, our results may provide novel clues for early diagnosis of carotid restenosis and developing new therapeutic strategy.

SUBMITTER: Luo T

PROVIDER: S-EPMC4221161 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Crosstalk between TGF-β/Smad3 and BMP/BMPR2 signaling pathways via miR-17-92 cluster in carotid artery restenosis.

Luo Tao T Cui Shijun S Bian Chunjing C Yu Xiaochun X

Molecular and cellular biochemistry 20131231 1-2

In the recent decades, carotid angioplasty and stenting (CAS) has been developed into a credible option for the patients with carotid stenosis. However, restenosis remains a severe and unsolved issue after CAS treatment. Restenosis is characterized by neointimal hyperplasia, which is partially caused by vascular smooth muscle cells (VSMC) proliferation. However, the molecular mechanism involved in the restenosis is still unclear. In this study, we demonstrated a functional crosstalk between two ...[more]

PMID: 24378993

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Project description:PurposeWe aimed to evaluate the long-term outcome of carotid endarterectomy (CEA) and carotid artery stenting (CAS) in patients who underwent both procedures on different sides.MethodsIn this single-center retrospective study (2001-2019), 117 patients (men, N = 78; median age at CEA, 64.4 [interquartile range {IQR}, 57.8-72.2] years; median age at CAS, 68.8 [IQR, 61.0-76.0] years) with ≥50% internal carotid artery stenosis who had CEA on one side and CAS on the other side were included. The risk of restenosis was estimated by treatment adjusted for patient and lesion characteristics.ResultsNeurological symptoms were significantly more common (41.9% vs 16.2%, P<0.001) and patients had a significantly shorter mean duration of smoking (30.2 [standard deviation {SD}, 22.2] years vs 31.8 [SD, 23.4] years, P<0.001), hypertension (10.1 [SD, 9.8] years vs 13.4 [SD, 9.1] years, P<0.001), hyperlipidemia (3.6 [SD, 6.6] years vs 5.0 [SD, 7.3] years, P = 0.001), and diabetes mellitus (3.9 [SD, 6.9] years vs 5.7 [SD, 8.9] years, P<0.001) before CEA compared to those before CAS. While the prevalence of heavily calcified stenoses on the operated side (25.6% vs 6.8%, P<0.001), the incidence of predominantly echogenic/echogenic plaques (53.0% vs 70.1%, P = 0.011) and suprabulbar lesions (1.7% vs 22.2%, P<0.001) on the stented side was significantly higher. Restenosis rates were 10.4% at 1 year, 22.3% at 5 years, and 33.7% at the end of the follow-up (at 11 years) for CEA, while these were 11.4%, 14.7%, and 17.2%, respectively, for CAS. Cox regression analysis revealed a significantly higher risk of restenosis (hazard ratio [HR], 1.80; 95% confidence interval [CI], 1.05-3.10; P = 0.030) for CEA compared to that for CAS. After adjusting for relevant confounding factors (smoking, hypertension, diabetes mellitus, calcification severity, plaque echogenicity, and lesion location), the estimate effect size materially did not change, although it did not remain statistically significant (HR, 1.85; 95% CI, 0.95-3.60; P = 0.070).ConclusionIntra-patient comparison of CEA and CAS in terms of restenosis tilts the balance toward CAS.

Project description:In the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the composite primary endpoint of stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke thereafter did not differ between carotid artery stenting and carotid endarterectomy for symptomatic or asymptomatic carotid stenosis. A secondary aim of this randomised trial was to compare the composite endpoint of restenosis or occlusion.Patients with stenosis of the carotid artery who were asymptomatic or had had a transient ischaemic attack, amaurosis fugax, or a minor stroke were eligible for CREST and were enrolled at 117 clinical centres in the USA and Canada between Dec 21, 2000, and July 18, 2008. In this secondary analysis, the main endpoint was a composite of restenosis or occlusion at 2 years. Restenosis and occlusion were assessed by duplex ultrasonography at 1, 6, 12, 24, and 48 months and were defined as a reduction in diameter of the target artery of at least 70%, diagnosed by a peak systolic velocity of at least 3·0 m/s. Studies were done in CREST-certified laboratories and interpreted at the Ultrasound Core Laboratory (University of Washington). The frequency of restenosis was calculated by Kaplan-Meier survival estimates and was compared during a 2-year follow-up period. We used proportional hazards models to assess the association between baseline characteristics and risk of restenosis. Analyses were per protocol. CREST is registered with ClinicalTrials.gov, number NCT00004732.2191 patients received their assigned treatment within 30 days of randomisation and had eligible ultrasonography (1086 who had carotid artery stenting, 1105 who had carotid endarterectomy). In 2 years, 58 patients who underwent carotid artery stenting (Kaplan-Meier rate 6·0%) and 62 who had carotid endarterectomy (6·3%) had restenosis or occlusion (hazard ratio [HR] 0·90, 95% CI 0·63-1·29; p=0·58). Female sex (1·79, 1·25-2·56), diabetes (2·31, 1·61-3·31), and dyslipidaemia (2·07, 1·01-4·26) were independent predictors of restenosis or occlusion after the two procedures. Smoking predicted an increased rate of restenosis after carotid endarterectomy (2·26, 1·34-3·77) but not after carotid artery stenting (0·77, 0·41-1·42).Restenosis and occlusion were infrequent and rates were similar up to 2 years after carotid endarterectomy and carotid artery stenting. Subsets of patients could benefit from early and frequent monitoring after revascularisation.National Institute of Neurological Disorders and Stroke and Abbott Vascular Solutions.

Project description:This study aimed to describe the duplex ultrasound (DUS) findings associated with carotid restenosis after carotid endarterectomy (CEA) and to determine whether carotid restenosis is associated with the clinical outcomes of CEA. Between January 2007 and December 2016, a total of 660 consecutive patients who underwent 717 CEAs were followed up at our hospital with DUS surveillance for at least 3 years after CEA. These patients were analyzed retrospectively for this study. Following CEA, restenosis was defined as the development of ≥50% stenosis, diagnosed on the basis of DUS findings of the luminal narrowing and velocity criteria. The study outcomes were defined as restenosis of the ipsilateral carotid artery after CEA and late (>30days) fatal or nonfatal stroke ipsilateral to the carotid restenosis. During the median follow-up period of 74 months, the restenosis incidence was 2.8% (20/717), and there were 2 strokes (2/20, 10%) ipsilateral to the restenosis after CEA; reintervention was performed for 11 patients with carotid restenosis (55%). Within 2 years after CEA, restenosis was identified in 9 cases (45%, 9/20), and 8 reinterventions (72.7%, 8/11) were performed. According to DUS findings, the morphologic characteristics of carotid restenosis were different from the preoperative plaque morphology. Among the 20 carotid restenosis cases, we observed the following DUS patterns: homogenous isoechoic restenosis (n = 14, 70%), homogenous hypoechoic (n = 2, 10%), isoechoic with hypoechoic surface (n = 3, 15%), and hypoechoic with isoechoic surface (n = 1, 5%). Although 9 carotid restenosis patients received prophylactic reintervention to mitigate the progression of restenosis, the 2 symptomatic restenosis patients had isoechoic lesions with hypoechoic surfaces on DUS. On Kaplan-Meier survival analyses, in terms of stroke-free survival rates, there was a higher risk of stroke among patients with carotid restenosis compared with patients without restenosis, with a non-significant trend (P = 0.051). In conclusion, most carotid restenoses were identified within 2 years after CEA, and there was a non-significant trend toward a higher risk of stroke among patients with carotid restenosis.

Dataset Information

Crosstalk between TGF-?/Smad3 and BMP/BMPR2 signaling pathways via miR-17-92 cluster in carotid artery restenosis.

Publications

Crosstalk between TGF-β/Smad3 and BMP/BMPR2 signaling pathways via miR-17-92 cluster in carotid artery restenosis.

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