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Gene expression in carotid stenosis

Yafei Li, Zhiyong Xie, Lei Chen, Jianjun Yan, Yao Ma, Liansheng Wang, Zhong Chen
BACKGROUND: Early B-cell factor 1 (EBF1) is a transcription factor expressed primarily during early B cell development. Previous studies have shown EBF1 regulates blood glucose and lipid metabolism in mice with diabetes and central adiposity. Recently, a genetic variation (rs36071027) located in an EBF1 gene intron was associated with carotid artery intima-media thickness. However, whether this polymorphism is actually linked with coronary artery disease (CAD) and its severity remains unclear...
February 10, 2017: BMC Cardiovascular Disorders
Juntao Hu, Jie Luo, Qianxue Chen
Moyamoya disease (MMD) is a cerebrovascular disease characterized by progressive stenosis of the intracranial internal carotid arteries and their proximal branches. Epidemiologically, MMD is more prevalent in east Asia than any region worldwide, which have been estimated at 0.94 per 100 000 in Japanese and 0.43 per 100,000 in Chinese.However, the etiology of this rare disease remains unknown. Regarding biomarkers of moyamoya disease, moyamoya disease is characterized by an increased expression of angiogenic factors and pro-inflammatory molecules such as vascular endothelial growth factors and matrix metalloproteinase-9, which may partly explain its clinical manifestations of the pathologic angiogenesis, spontaneous hemorrhage, and higher incidence of cerebral hyperperfusion after revascularization surgery...
January 30, 2017: World Neurosurgery
Suzanne M Eken, Hong Jin, Ekaterina Chernogubova, Yuhuang Li, Nancy Simon, Changyan Sun, Greg Korzunowicz, Albert Busch, Alexandra Bäcklund, Cecilia Österholm, Anton Razuvaev, Thomas Renné, Hans-Henning Eckstein, Jaroslav Pelisek, Per Eriksson, Maria Gonzalez Diez, Ljubica P Matic Perisic, Isabel N Schellinger, Uwe Raaz, Nicholas J Leeper, Göran K Hansson, Gabrielle Paulsson-Berne, Ulf Hedin, Lars Maegdefessel
RATIONALE: In the search for markers and modulators of vascular disease, miRNAs have emerged as potent therapeutic targets. OBJECTIVE: To investigate miRNAs of clinical interest in patients with unstable carotid stenosis at risk of stroke. METHODS AND RESULTS: Utilizing patient material from the Biobank of Karolinska Endarterectomies (BiKE), we profiled miRNA expression in patients with stable vs unstable carotid plaque. A PCR-based miRNA array of plasma, sampled at the carotid lesion site, identified eight deregulated miRNAs (miR-15b, -29c, -30c/d, -150, -191, -210 and -500)...
November 28, 2016: Circulation Research
Soto Romuald Kiando, Nathan R Tucker, Luis-Jaime Castro-Vega, Alexander Katz, Valentina D'Escamard, Cyrielle Tréard, Daniel Fraher, Juliette Albuisson, Daniella Kadian-Dodov, Zi Ye, Erin Austin, Min-Lee Yang, Kristina Hunker, Cristina Barlassina, Daniele Cusi, Pilar Galan, Jean-Philippe Empana, Xavier Jouven, Anne-Paule Gimenez-Roqueplo, Patrick Bruneval, Esther Soo Hyun Kim, Jeffrey W Olin, Heather L Gornik, Michel Azizi, Pierre-François Plouin, Patrick T Ellinor, Iftikhar J Kullo, David J Milan, Santhi K Ganesh, Pierre Boutouyrie, Jason C Kovacic, Xavier Jeunemaitre, Nabila Bouatia-Naji
Fibromuscular dysplasia (FMD) is a nonatherosclerotic vascular disease leading to stenosis, dissection and aneurysm affecting mainly the renal and cerebrovascular arteries. FMD is often an underdiagnosed cause of hypertension and stroke, has higher prevalence in females (~80%) but its pathophysiology is unclear. We analyzed ~26K common variants (MAF>0.05) generated by exome-chip arrays in 249 FMD patients and 689 controls. We replicated 13 loci (P<10-4) in 402 cases and 2,537 controls and confirmed an association between FMD and a variant in the phosphatase and actin regulator 1 gene (PHACTR1)...
October 2016: PLoS Genetics
Jian Dong, Chao Song, Lei Zhang, Xiang Feng, Rui Feng, Qingsheng Lu, Zhiqing Zhao, Junmin Bao, Jian Zhou, Zaiping Jing
As one of the leading reason in morbidity and death in the world, atherosclerosis is usually associated with vessel stenosis, ulceration, and inflammatory cell infiltration. However, the formation mechanism of atheroma plaque is unknown. In this research, we have used bioinformatics tools to identify 118 differential expression genes from a GEO dataset. Besides, we also revealed KYNU as a crucial gene in atheroma plaque development.
August 12, 2016: Artificial Cells, Nanomedicine, and Biotechnology
Farima Zahedi, Maliheh Nazari-Jahantigh, Zhe Zhou, Pallavi Subramanian, Yuanyuan Wei, Jochen Grommes, Stefan Offermanns, Sabine Steffens, Christian Weber, Andreas Schober
MicroRNAs (miRNAs) coordinate vascular repair by regulating injury-induced gene expression in vascular smooth muscle cells (SMCs) and promote the transition of SMCs from a contractile to a proliferating phenotype. However, the effect of miRNA expression in SMCs on neointima formation is unclear. Therefore, we studied the role of miRNA biogenesis by Dicer in SMCs in vascular repair. Following wire-induced injury to carotid arteries of Apolipoprotein E knockout (Apoe (-/-)) mice, miRNA microarray analysis revealed that the most significantly regulated miRNAs, such as miR-222 and miR-21-3p, were upregulated...
January 2017: Cellular and Molecular Life Sciences: CMLS
Zhen-Hua Zhou, Jing Peng, Zhao-You Meng, Lin Chen, Jia-Lu Huang, He-Qing Huang, Li Li, Wen Zeng, Yong Wei, Chu-Hong Zhu, Kang-Ning Chen
BACKGROUND: Carotid artery stenosis is a major risk factor for ischemic stroke. Although carotid angioplasty and stenting using an embolic protection device has been introduced as a less invasive carotid revascularization approach, in-stent restenosis limits its long-term efficacy and safety. The objective of this study was to test the anti-restenosis effects of local stent-mediated delivery of the A20 gene in a porcine carotid artery model. MATERIALS AND METHODS: The pCDNA3...
2016: Drug Design, Development and Therapy
S Kiando, N Tucker, L Castro-Vega, D Cusi, P Galan, Empana J-P, J Olin, H Gornik, P-F Plouin, I Kullo, D Milan, S Ganesh, P Boutouyrie, J Kovacic, X Jeunemaitre, N Bouatia-Naji
OBJECTIVE: Fibromuscular dysplasia (FMD) is a nonatherosclerotic vascular disease leading to stenosis, dissection and aneurysm affecting mainly the renal and cerebrovascular arteries. FMD has higher prevalence in females (80-90%) and predisposes to hypertension and stroke but its pathophysiology is unclear. DESIGN AND METHOD: We performed a multistage genetic association study (1,154 patients and 3,895 controls) from five case-control cohorts. We investigated the association between rs9349379 in the phosphatase and actin regulator 1 gene (PHACTR1) and carotid traits by echo-tracking in healthy volunteers, the expression of PHACTR1 by genotypes in human fibroblasts, protein staining pattern in human carotids, and vasculature development after Phactr1 knockdown in zebrafish...
September 2016: Journal of Hypertension
J-M Daniel, C A Reichel, T Schmidt-Woell, J Dutzmann, G Zuchtriegel, F Krombach, J Herold, J Bauersachs, D G Sedding, S M Kanse
Essentials Factor VII-activating protease (FSAP) is a plasma protease involved in vascular processes. Neointima formation was investigated after vascular injury in FSAP(-/-) mice. The neointimal lesion size and the accumulation of macrophages were increased in FSAP(-/-) mice. This was due to an increased activity of the chemokine (C-C motif) ligand 2 (CCL2). SUMMARY: Background Factor VII-activating protease (FSAP) is a multifunctional circulating plasma serine protease involved in thrombosis and vascular remodeling processes...
October 2016: Journal of Thrombosis and Haemostasis: JTH
Sung Min Ahn, Yu Ri Kim, Ha Neui Kim, Yong-Il Shin, Hwa Kyoung Shin, Byung Tae Choi
We modeled prolonged cerebral hypoperfusion in mice using bilateral common carotid artery stenosis (BCAS) and electroacupuncture (EA) stimulation was applied at two acupoints, Baihui (GV20) and Dazhui (GV14). In behavioral tests of memory, BCAS produced impairments in spatial and short-term memory in mice that were attenuated by therapeutic EA stimulation. Therapeutic use of EA in BCAS also enhanced oligodendrocyte (OL) differentiation from oligodendrocyte precursor cells (OPCs), in association with white matter improvements in the corpus callosum (CC)...
2016: Scientific Reports
Ming Tan, Hong-Bing Yan, Jian-Nan Li, Wen-Ke Li, Yuan-Yuan Fu, Wen Chen, Zhou Zhou
BACKGROUND/AIMS: It is difficult to predict acute thrombotic cardiovascular events in the clinic. Few studies have reported the presence of plasma exosomes containing microRNAs (miRNAs) in cardiovascular events. Therefore, we aimed to investigate the levels of miR-223, miR-339 and miR-21 in plasma exosomes before thrombosis in mouse models of carotid tandem stenosis, as well as the mechanisms underlying the origin and function of these exosomal miRNAs. METHODS: Plasma samples were collected from the carotid tandem stenosis and sham control groups of our successfully developed atherothrombosis mouse models before thrombosis...
2016: Cellular Physiology and Biochemistry
Rajiv Janardhanan, Binxia Yang, Sreenivasulu Kilari, Edward B Leof, Debabrata Mukhopadhyay, Sanjay Misra
PURPOSE: To determine if a second dose of a lentivirus mediated small hairpin RNA that inhibits Vegf-A gene expression (LV-shRNA-Vegf-A) can improve lumen vessel area (LVA) of the outflow vein of an arteriovenous fistula (AVF) and decrease venous neointimal hyperplasia. MATERIALS AND METHODS: Chronic kidney disease was created in C57BL/6 mice; 28 days later, an AVF was created by connecting the right carotid artery to the ipsilateral jugular vein. Immediately after AVF creation, 5 × 10(6) plaque-forming units of LV-shRNA-Vegf-A or control shRNA was administered to the adventitia of the outflow vein, and a second dose of the same treatment was administered 14 days later...
April 2016: Journal of Vascular and Interventional Radiology: JVIR
S Kiando, N Tucker, A Katz, C Tréard, V Desca-Mard, L Castro-Vega, C Barlasina, D Cusi, P Galan, J Empana, J Olin, H Gornik, P Plouin, I Kullo, D Milan, S Ganesh, P Boutouyrie, J Kovacic, X Jeunemaitre, N Bouatia-Naji
BACKGROUND: Fibromuscular dysplasia (FMD) is a nonatherosclerotic vascular disease leading to arterial stenosis, aneurysm and dissection, mainly in renal and carotid artery. FMD has higher prevalence in females (80-90%) and is associated with hypertension and stroke. The pathophysiology of FMD is unclear and a genetic origin is suspected. METHODS: We performed a genetic association study in European ancestry individuals. The discovery included 249 cases and 689 controls, in which we analyzed 25,606 common variants (MAF>0...
December 2015: Annales de Cardiologie et D'angéiologie
Yu Zhang, Lin Cheng, Yajing Chen, Guo-Yuan Yang, Jianrong Liu, Lili Zeng
OBJECTIVE: We aim to explore the clinical factors and blood biomarker for predicting the early-onset post-stroke depression (PSD). METHODS: 251 acute ischemic stroke patients were divided into PSD group and non-PSD group by Hamilton depression scale in 2 weeks after stroke. The clinical data, the severity, etiology and location of stroke were recorded. The analysis of inflammatory mediator, glycose and lipid metabolism was performed on the day of admission. The association between clinical factors and early onset PSD was studied by logistic regression analysis...
March 15, 2016: Journal of Affective Disorders
L Perisic, S Aldi, Y Sun, L Folkersen, A Razuvaev, J Roy, M Lengquist, S Åkesson, C E Wheelock, L Maegdefessel, A Gabrielsen, J Odeberg, G K Hansson, G Paulsson-Berne, U Hedin
BACKGROUND: Embolism from unstable atheromas in the carotid bifurcation is a major cause of stroke. Here, we analysed gene expression in endarterectomies from patients with symptomatic (S) and asymptomatic (AS) carotid stenosis to identify pathways linked to plaque instability. METHODS: Microarrays were prepared from plaques (n = 127) and peripheral blood samples (n = 96) of S and AS patients. Gene set enrichment, pathway mapping and network analyses of differentially expressed genes were performed...
March 2016: Journal of Internal Medicine
Nicole J Ullrich, Leslie B Gordon
Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare, uniformly fatal, segmental "premature aging" disease in which children exhibit phenotypes that may give us insights into the aging process at both the cellular and organismal levels. Initial presentation in early childhood is primarily based on growth and dermatologic findings. Primary morbidity and mortality for children with HGPS is from atherosclerotic cardiovascular disease and strokes with death occurring at an average age of 14.6 years...
2015: Handbook of Clinical Neurology
Mingyu Shi, Feng Yin, Hongyue Gu, Jing Zhu, Xinhua Yin
INTRODUCTION: Our aim was to study the efficacy and safety of tissue factor pathway inhibitor (TFPI)-coated stents in inhibiting restenosis in a rabbit carotid artery model. METHODS: Subculture was conducted in aorta smooth muscle cell, which was taken from male Wistar rat, and the 3-5-generation cells were taken for plasmid transfection and cytotoxicity experiment. TFPI microspheres were made of a TFPI plasmid which was enwrapped by poly-l-glutamic acid (PLGA)...
December 2015: Cardiovascular Therapeutics
Velidi H Rao, Vikrant Rai, Samantha Stoupa, Devendra K Agrawal
Although degradation of extracellular matrix by matrix metalloproteinases (MMPs) is thought to be involved in symptomatic (S) carotid plaques in atherosclerosis, the mechanisms of MMP expression are poorly understood. Here, we demonstrate that collagen loss in vascular smooth vessel cells (VSMCs) isolated from S plaques was induced by epidermal growth factor (EGF) through the activation of p38-MAPK and JNK-MAPK pathways. Inhibitors of p38-MAPK and JNK-MAPK signaling pathways downregulated the expression of MMP-1 and MMP-9...
September 15, 2015: American Journal of Physiology. Heart and Circulatory Physiology
Wenya Lan, Fang Yang, Zhuangli Li, Ling Liu, Hongfei Sang, Yongjun Jiang, Yunyun Xiong, Renliang Zhang
OBJECTIVE: Effective treatments against restenosis after percutaneous transluminal angioplasty and stenting are largely lacking. Human tissue kallikrein gene transfer has been shown to be able to attenuate neointima formation induced by balloon catheter. As a tissue kallikrein in vivo, human urinary kininogenase (HUK) is widely used to prevent ischemia-reperfusion injury. However, the effects of HUK on neointima formation have not been explored. We therefore investigated whether HUK could alleviate balloon catheter-induced intimal hyperplasia in rabbits fed with high-fat diets...
October 2016: Journal of Vascular Surgery
Hong Ran, Wei Duan, Zili Gong, Senlin Xu, He Zhu, Xianhua Hou, Li Jiang, Qifen He, Jian Zheng
Adenosine A2A receptors (A2ARs) in distinct cellular types may exert different and even opposite effects on many neurologic disorders; A2ARs in bone marrow-derived cells (BMDCs) have been shown to play important roles in various brain injuries. We previously showed that global A2AR inactivation aggravates chronic cerebral hypoperfusion-induced white matter lesions (WMLs); however, the specific cell populations responsible for A2AR-mediated signaling remain unknown. In the present study, we developed chimeric mice in which A2ARs were either selectively inactivated or reconstituted in BMDCs by transplanting bone marrow from global A2AR gene knockout or wild-type mice into wild-type or gene knockout mice, respectively...
April 2015: Journal of Neuropathology and Experimental Neurology
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