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Gene expression in carotid stenosis

Russell Knutsen, Scott C Beeman, Thomas J Broekelmann, Delong Liu, Kit Man Tsang, Attila Kovacs, Li Ye, Joshua Danback, Anderson Watson, Amanda Wardlaw, Jessica Wagenseil, Joel R Garbow, Michael Shoykhet, Beth A Kozel
Increased vascular stiffness correlates with higher risk of cardiovascular complications in aging adults. Elastin insufficiency, as observed in patients with Williams-Beuren syndrome or with familial supravalvular aortic stenosis, also increases vascular stiffness and leads to arterial narrowing. We used Eln+/- mice to test the hypothesis that pathologically increased vascular stiffness with concomitant arterial narrowing leads to decreased blood flow to end organs such as the brain. We also hypothesized that drugs which remodel arteries and increase lumen diameter would improve flow...
March 2, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Berk Arapi, Burcu Bayoğlu, Müjgan Cengiz, Ahmet Dirican, Serkan Burç Deser, Yerik Junusbekov, Caner Arslan
BACKGROUND: Carotid artery stenosis (CAS) is the atherosclerotic narrowing of the proximal internal carotid artery (ICA) and one of the main causes of stroke. Elevated expression of the pleiotropic proinflammatory cytokine, interleukin-18 (IL18), has been shown in human atherosclerotic plaques. AIMS: To investigate whether IL18 and interleukin-18 binding protein (IL18BP) mRNA expression and IL18 -137 G/C (rs187238) variants are associated with CAS development. STUDY DESIGN: Case-control study...
February 27, 2018: Balkan Medical Journal
Chrissta X Maracle, Rabia Agca, Boy Helder, John A L Meeuwsen, Hans W M Niessen, Erik A L Biessen, Menno P J de Winther, Saskia C A de Jager, Mike T Nurmohamed, Sander W Tas
BACKGROUND AND AIMS: Neovascularization is associated with atherosclerotic plaque instability and increased chance of myocardial infarction (MI). Patients with chronic inflammatory diseases (CID) have increased risk of atherosclerosis, and evidence demonstrates that NF-κB inducing kinase (NIK)-mediated noncanonical NF-κB signaling in endothelial cells (EC) is linked to inflammation and angiogenesis. Here, we hypothesized NIK may also be activated in EC of atherosclerotic lesion microvessels...
January 29, 2018: Atherosclerosis
Lian Duan, Ling Wei, Yanghua Tian, Zhengshan Zhang, Panpan Hu, Qiang Wei, Sugang Liu, Jun Zhang, Yuyang Wang, Desheng Li, Weizhong Yang, Rui Zong, Peng Xian, Cong Han, Xiangyang Bao, Feng Zhao, Jie Feng, Wei Liu, Wuchun Cao, Guoping Zhou, Chunyan Zhu, Fengqiong Yu, Weimin Yang, Yu Meng, Jingye Wang, Xianwen Chen, Yu Wang, Bing Shen, Bing Zhao, Jinghai Wan, Fengyu Zhang, Gang Zhao, Aimin Xu, Xuejun Zhang, Jianjun Liu, Xianbo Zuo, Kai Wang
BACKGROUND AND PURPOSE: Moyamoya disease (MMD) is a rare cerebral vasculopathy characterized by bilateral internal carotid artery stenosis and often leads to stroke in children or young adults. Although familial inheritance is well recognized, the genetic basis of MMD remains poorly understood. METHODS: A 2-stage genome-wide association study was conducted involving 1492 cases and 5084 controls. In the discovery stage, logistic regression was used to test associations, and imputation was conducted based on genotyped single-nucleotide polymorphisms (SNPs)...
January 2018: Stroke; a Journal of Cerebral Circulation
Ida Gregersen, Øystein Sandanger, Erik T Askevold, Ellen Lund Sagen, Kuan Yang, Sverre Holm, Turid M Pedersen, Mona Skjelland, Kirsten Krohg-Sørensen, Trond Vidar Hansen, Tuva Børresdatter Dahl, Kari Otterdal, Terje Espevik, Pål Aukrust, Arne Yndestad, Bente Halvorsen
AIM: Interleukin-27 (IL-27) is involved in different inflammatory diseases; however, its role in atherosclerosis is unclear. In this study we investigated the expression of IL-27 and its receptor in patients with carotid atherosclerosis and if IL-27 could modulate the inflammatory effects of the NLRP3 inflammasome in vitro. METHODS: Plasma IL-27 was measured by enzyme immunoassay in patients with carotid stenosis (n = 140) and in healthy controls (n = 19). Expression of IL-27 and IL-27R was analyzed by quantitative PCR and immunohistochemistry in plaques from patients and in non-atherosclerotic vessels...
2017: PloS One
Miki Fujimura, Taku Fujimura, Aya Kakizaki, Mika Sato-Maeda, Kuniyasu Niizuma, Yasutake Tomata, Setsuya Aiba, Teiji Tominaga
Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by a progressive stenosis at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Although its etiology is still unknown, intrinsic immune reactions such as autoimmune response has been implicated in the pathogenesis of MMD. Recently, the RING finger protein 213 (RNF213) was found to be an important risk gene for MMD, and is predominantly expressed in blood cells and the spleen. Thus, we hypothesized that patients with MMD represent an intrinsic autoimmune status mediated by M2-polarized macrophages, which play an important role in tissue remodeling and angiogenesis...
January 15, 2018: Brain Research
Ryo Ohtomo, Taro Bannai, Gaku Ohtomo, Akihiro Shindo, Hidekazu Tomimoto, Shoji Tsuji, Atsushi Iwata
Cilostazol is known to alleviate white matter demyelination due to chronic cerebral hypoperfusion in rodent models, although their pharmacological mechanisms remain unclear. In this study, we investigated the protective effect of cilostazol in relation to gene expression profile. Bilateral common carotid artery stenosis (BCAS) mice were treated with oral administration of cilostazol or placebo starting from a week after the surgery. Demyelination of the cingulum was compared between the 2 groups 2, 6, and 10 weeks after initial drug administration...
October 27, 2017: Neuroscience Letters
Yan Zhang, Yaolei Zhang, Wei Li, Peijian Wang, Rui Gu, Yaxing Feng, Shujie Wei, Ke Peng, Yunrong Zhang, Linan Su, Qiang Wang, De Li, Dachun Yang, Wing Tak Wong, Yongjian Yang, Shuangtao Ma
BACKGROUND: Intracoronary stent restenosis, characterized by excessive smooth muscle cell (SMC) proliferation and myointimal hyperplasia, remains a clinical challenge. Mitochondrial membrane potential has been linked to the proliferative rate of SMCs. This study aimed to screen a critical gene regulating mitochondrial potential and to confirm its effects on myointimal formation in preclinical animal models. METHODS AND RESULTS: We performed transcriptome screening for genes differentially expressed in ligated versus unligated mouse carotid arteries...
October 12, 2017: Journal of the American Heart Association
Feng Jin, Kai Wang, Xiaochuan Sun, Zhanpu Zhang, Ping Han
The present study analyzed gene expression arrays to identify differentially-expressed genes (DEGs) between mycophenolate mofetil (MMF)‑treated and placebo‑treated patients with symptomatic carotid artery stenosis (SCAS). In addition, the key genes involved in the pharmacology of MMF treatment in patients with SCAS were identified. The gene expression dataset was obtained from a Gene Expression Omnibus database, which included 9 MMF‑treated and 11 placebo‑treated samples. The DEGs were identified between MMF and placebo groups using R software...
November 2017: Molecular Medicine Reports
Kristina Byskov, Thomas Boettger, Paul F Ruehle, Nis Valentin Nielsen, Michael Etscheid, Sandip M Kanse
BACKGROUND AND AIMS: The factor VII activating protease (FSAP) knockout mice have a bigger neointima after vascular injury and a larger infarct volume after stroke. The Marburg I (MI) single nucleotide polymorphism (SNP) in the FSAP-encoding gene is associated with an increased risk of stroke and carotid stenosis in humans. We hypothesize that the regulation of gene expression by FSAP in vascular cells accounts for its vasculo-regulatory properties. METHODS: Vascular smooth muscle cells (VSMC) and endothelial cells (EC) were stimulated with FSAP and a microarray-based expression analysis was performed...
August 25, 2017: Atherosclerosis
Mika Sato-Maeda, Miki Fujimura, Sherif Rashad, Yuiko Morita-Fujimura, Kuniyasu Niizuma, Hiroyuki Sakata, Shuntaro Ikawa, Teiji Tominaga
The RING finger protein 213 (RNF213) is an important susceptibility gene for moyamoya disease (MMD) and is also implicated in other types of intracranial major artery stenosis/occlusion (ICAS); however, the role of RNF213 in the development of ICAS including MMD is unclear. The constitutive expression of the RNF213 gene is relatively weak in brain tissue, while information regarding the expression patterns of the RNF213 gene under cerebral ischemia, which is one of characteristic pathologies associated with ICAS, is currently limited...
September 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
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 other region worldwide, and has been estimated at 0.94 per 100,000 in the Japanese and 0.43 per 100,000 in the Chinese population. The etiology of this rare disease, however, remains unknown. Regarding biomarkers, MMD is characterized by an increased expression of angiogenic factors and proinflammatory 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 greater incidence of cerebral hyperperfusion after revascularization surgery...
May 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, María González Díez, Ljubica Perisic Matic, 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, microRNAs (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: Using patient material from the BiKE (Biobank of Karolinska Endarterectomies), we profiled miRNA expression in patients with stable versus unstable carotid plaque. A polymerase chain reaction-based miRNA array of plasma, sampled at the carotid lesion site, identified 8 deregulated miRNAs (miR-15b, miR-29c, miR-30c/d, miR-150, miR-191, miR-210, and miR-500)...
February 17, 2017: 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.
September 2017: 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
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