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Mmp aneurysm

Hugo Alberto Rojas, Karla Simone da Silva Fernandes, Mariana Rodrigues Ottone, Kênia Cristina S Fonseca de Magalhães, Lucas Alverne Albuquerque, Julio Leonardo Barbosa Pereira, Gerival Vieira Júnior, José Lopes Sousa-Filho, Bruno Silva Costa, Valéria Cristina Sandrim, Marcos Dellaretti, Renata Toscano Simões
BACKGROUND: Intracranial aneurysms are arterial anomalies affecting 2% to 3% of the general population in the world and these ruptures are associated with a high mortality. Some risk factors, such as age, gender, smoking, alcohol, hypertension and familial history are associated with the number of aneurysms and their size. In addition, inflammatory processes within the blood vessels of the brain can activate matrix metalloproteinase-9 (MMP-9), which degrades various components of the extracellular matrix, such as elastin...
March 5, 2018: Clinical Biochemistry
Zhidong Zhang, Kai Liang, Gangqiang Zou, Xiaosan Chen, Shuaitao Shi, Guoquan Wang, Kewei Zhang, Kun Li, Shuiting Zhai
The aim of this study was to identify abdominal aortic aneurysms (AAA)-associated miR-155 contributing to AAA pathology by regulating macrophage-mediated inflammation. Angiotensin II (AngII)-infused apolipoprotein E-deficient (ApoE-/-) mice and THP-1 cells model of miR-155 over-expression and deficiency were used in the experiments. The expression of miR-155 was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cytokines were evaluated using enzyme-linked immunoabsorbent assay (ELISA)...
February 19, 2018: Bioscience Reports
Peixi Liu, Yaying Song, Yingjie Zhou, Yingjun Liu, Tianming Qiu, Qingzhu An, Jianping Song, Peiliang Li, Yuan Shi, Sichen Li, Kai Quan, Guo-Yuan Yang, Wei Zhu
BACKGROUND/AIMS: Cerebral aneurysm growth is characterized by continuous structural weakness of local smooth muscle cells, though the mechanism is unclear. In this study, we examine protein changes in cerebral aneurysm and human brain vascular smooth muscle cells after cyclic mechanical stretch. We further explore the relationship between the smooth muscle cell changes and reductions in the levels of collagen types IV and VI. METHODS: Saccular cerebral aneurysms (n=10) were collected, and temporal artery samples were used as controls...
February 7, 2018: Cellular Physiology and Biochemistry
Antonio Di Gennaro, Ana Carolina Araújo, Albert Busch, Hong Jin, Dick Wågsäter, Emina Vorkapic, Kenneth Caidahl, Per Eriksson, Bengt Samuelsson, Lars Maegdefessel, Jesper Z Haeggström
Cysteinyl-leukotrienes (cys-LTs) are 5-lipoxygenase-derived lipid mediators involved in the pathogenesis and progression of inflammatory disorders, in particular asthma. We have previously found evidence linking these mediators to increased levels of proteolytic enzymes in tissue specimens of human abdominal aortic aneurysm (AAA). Here we show that antagonism of the CysLT1 receptor by montelukast, an established antiasthma drug, protects against a strong aorta dilatation (>50% increase = aneurysm) in a mouse model of CaCl 2 -induced AAA at a dose comparable to human medical practice...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Xiaohui Ma, Hairong Yao, Yuhong Yang, Long Jin, Yu Wang, Lina Wu, Shengli Yang, Kang Cheng
In the present study, the function of microRNA (miR)‑195 on abdominal aortic aneurysm (AAA) and its possible mechanism were investigated. Reverse transcription‑quantitative polymerase chain reaction analysis was used to detect the expression of miR‑195 in patients with AAA. The expression levels of miR‑195 in patients with AAA were effectively increased. The present study also used miR‑195 mimics to increase the expression of miR‑195, and ELISA kits and western blot analysis were used to analyze the levels of interleukin (IL)‑1β and IL‑6, and the protein expression levels of matrix metalloproteinase (MMP)‑2, MMP‑9, tumor necrosis factor (TNF)‑α, nuclear factor (NF)‑κB, vascular endothelial growth factor (VEGF), phosphoinositide 3‑kinase (PI3K) and phosphorylated (p‑)Akt...
January 25, 2018: International Journal of Molecular Medicine
Keisuke Hashimoto, Hirona Kugo, Hiroki Tanaka, Kazuko Iwamoto, Chie Miyamoto, Tetsumei Urano, Naoki Unno, Kohsuke Hayamizu, Nobuhiro Zaima, Tatsuya Moriyama
Abdominal aortic aneurysm (AAA) is a vascular disease characterized by chronic inflammation in the infrarenal aorta. Most cases of AAA remain asymptomatic until rupture, and the mortality rate of patients with AAA rupture is very high. Currently, the relation between dietary habits and AAA development remains unknown. In this study, we evaluated the effects of a high-fat diet on the development of AAA in a vascular hypoperfusion-induced animal model. The risk of AAA rupture and AAA diameter in the high-fat group significantly increased compared with those in the control group...
January 29, 2018: Journal of Vascular Research
Varinder S Alg, Xiayi Ke, Joan Grieve, Stephen Bonner, Daniel C Walsh, Diederik Bulters, Neil Kitchen, Henry Houlden, David J Werring
INTRODUCTION: Abnormalities in Matrix Metalloproteinase (MMP) genes, which are important in extracellular matrix (ECM) maintenance and therefore arterial wall integrity are a plausible underlying mechanism of intracranial aneurysm (IA) formation, growth and subsequent rupture. We investigated whether the rs243865 C > T SNP (single nucleotide polymorphism) within the MMP-2 gene (which influences gene transcription) is associated with IA compared to matched controls. MATERIALS AND METHODS: We conducted a case-control genetic association study, adjusted for known IA risk factors (smoking and hypertension), in a UK Caucasian population of 1409 patients with intracranial aneurysms (IA), and 1290 matched controls, to determine the association of the rs243865 C > T functional MMP-2 gene SNP with IA (overall, and classified as ruptured and unruptured)...
January 15, 2018: British Journal of Neurosurgery
Xi Wang, Raouf A Khalil
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that degrade various proteins in the extracellular matrix (ECM). Typically, MMPs have a propeptide sequence, a catalytic metalloproteinase domain with catalytic zinc, a hinge region or linker peptide, and a hemopexin domain. MMPs are commonly classified on the basis of their substrates and the organization of their structural domains into collagenases, gelatinases, stromelysins, matrilysins, membrane-type (MT)-MMPs, and other MMPs...
2018: Advances in Pharmacology
Ananth K Vellimana, Meng-Liang Zhou, Itender Singh, Diane J Aum, James W Nelson, Glenn R Harris, Umeshkumar Athiraman, Byung H Han, Gregory J Zipfel
Objective: Delayed cerebral ischemia (DCI) is an independent risk factor for poor outcome after aneurysmal subarachnoid hemorrhage (SAH) and is multifactorial in etiology. While prior studies have suggested a role for matrix metalloproteinase-9 (MMP-9) in early brain injury after SAH, its contribution to the pathophysiology of DCI is unclear. Methods: In the first experiment, wild-type (WT) and MMP-9 -/- mice were subjected to sham or endovascular perforation SAH surgery...
December 2017: Annals of Clinical and Translational Neurology
Shih-Hung Tsai, Jen-Chun Wang, Wen-I Liao, Yu-Juei Hsu, Chih-Yuan Lin, Min-Tser Liao, Po-Hsun Huang, Shing-Jong Lin
BACKGROUND: Rupture of abdominal aortic aneurysm (AAA) is one of the leading causes of sudden death among the elderly. Most incidental AAAs are below the threshold for intervention at the time of detection; however, there is no evidence that commonly used cardiovascular drugs have clinical beneficial effects on AAA progression. Therefore, in addition to current cardiovascular risk-reducing treatments, an adjunctive medical therapy targeting the regulation of extracellular matrix metabolism is still required in the clinical setting...
December 28, 2017: Journal of Vascular Surgery
Rawa Arif, Marcin Zaradzki, Anca Remes, Philipp Seppelt, Reiner Kunze, Hannes Schröder, Simon Schwill, Stephan M Ensminger, Peter N Robinson, Matthias Karck, Oliver J Müller, Markus Hecker, Andreas H Wagner, Klaus Kallenbach
Marfan syndrome is characterized by high expression of matrix metalloproteinases (MMPs) in aortic smooth muscle cells (AoSMCs) associated with medial elastolysis and aortic root aneurysm. We aimed to reduce aortic elastolysis through decrease of MMP expression with decoy oligodeoxynucleotides (dODNs) neutralizing the transcription factor activating factor-1 (AP-1). AP-1 abundance in nuclear extracts as well as MMP-2 and MMP-9 expression were significantly increased in isolated mAoSMC of mgR/mgR Marfan mice compared to wild-type cells...
December 15, 2017: Molecular Therapy. Nucleic Acids
Cressida A Lyon, Helen Williams, Rosaria Bianco, Steven J Simmonds, Bethan A Brown, Kerry S Wadey, Frank C T Smith, Jason L Johnson, Sarah J George
There is an unmet need for treatments to reduce abdominal aortic aneurysm (AAA) progression. Vascular smooth muscle cell (VSMC) apoptosis precipitates AAA formation, whereas VSMC proliferation repairs the vessel wall. We previously demonstrated that over-expression of EC4-Fc (truncated N-cadherin), or deletion of matrix-metalloproteinase-7 (Mmp-7) reduced VSMC apoptosis in mouse atherosclerotic plaques. Additionally, MMP-7 promotes VSMC apoptosis by cleavage of N-cadherin. We investigated their combined effect on AAA formation...
December 11, 2017: Scientific Reports
Rishi Batra, Melissa K Suh, Jeffrey S Carson, Matthew A Dale, Trevor M Meisinger, Matthew Fitzgerald, Patrick J Opperman, Jiangtao Luo, Iraklis I Pipinos, Wanfen Xiong, B Timothy Baxter
OBJECTIVE: Abdominal aortic aneurysms are inflammatory in nature and are associated with some risk factors that also lead to atherosclerotic occlusive disease, most notably smoking. The purpose of our study was to identify differential cytokine expression in patients with abdominal aortic aneurysm and those with atherosclerotic occlusive disease. Based on this analysis, we further explored and compared the mechanism of action of IL (interleukin)-1β versus TNF-α (tumor necrosis factor-α) in abdominal aortic aneurysm formation...
February 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Mark T Windsor, Tom G Bailey, Maria Perissiou, Kim Greaves, Pankaj Jha, Anthony S Leicht, Fraser D Russell, Jonathan Golledge, Christopher D Askew
PURPOSE: Inflammation and extracellular matrix degeneration contribute to abdominal aortic aneurysm (AAA) development. We aimed to assess the effect of exercise intensity on circulating biomarkers of inflammation and extracellular matrix degeneration in patients with AAA and healthy older adults. METHODS: Twenty patients with AAA (74±6y) and twenty healthy males (72±5y) completed moderate-intensity cycling at 40% peak power output (PPO), higher-intensity intervals at 70% PPO, and control (rest) on separate days...
November 27, 2017: Medicine and Science in Sports and Exercise
W-H Zhang, C-H Qiao, X Zhang, H Luo, X-K Sun
OBJECTIVE: To investigate the expression of matrix metalloproteinase-7 (MMP-7) in abdominal aortic aneurysm (AAA) with hypertension, and the clinical efficacy of endovascular exclusion. PATIENTS AND METHODS: Seventy-two cases of AAA with hypertension were retrospectively analyzed. Patients were divided into the observation group (34 cases) and control group (38 cases). The control group was treated by AAA incision with artificial vascular replacement, while the observation group was treated by endovascular graft exclusion...
October 2017: European Review for Medical and Pharmacological Sciences
Sonu Kashyap, Gina Warner, Zeng Hu, Feng Gao, Mazen Osman, Yousif Al Saiegh, Karen R Lien, Karl Nath, Joseph P Grande
Renovascular hypertension (RVH) has deleterious effects on both the kidney and the heart. TGF-β signaling through Smad3 directs tissue fibrosis in chronic injury models. In the 2-kidney 1-clip (2K1C) model of RVH, employing mice on the 129 genetic background, Smad3 deficiency (KO) protects the stenotic kidney (STK) from development of interstitial fibrosis. However, these mice have an increased incidence of sudden cardiac death following 2K1C surgery. The purpose of this study was to characterize the cardiovascular phenotype of these mice...
2017: PloS One
Takashi Miyake, Tetsuo Miyake, Hideo Shimizu, Ryuichi Morishita
Angiotensin II is thought to participate in aneurysm formation, because of its ability to induce and perpetuate inflammation in the aortic wall. Because activation of renin is the first step of the renin-angiotensin system, renin inhibition could inhibit all components of this system effectively. Therefore, we examined the hypothesis that direct inhibition of renin activity could decrease the expansion of aortic aneurysm using a rabbit model. Aortic dilatation was induced by incubation with elastase around the rabbit abdominal aorta...
December 2017: Hypertension
Xintong Zhang, Lei Chen, Feng Zheng, Yanli Du
The clinical efficacy of microsurgical neck clipping for the treatment of cerebral aneurysm rupture and its effect on serum nuclear factor κ-light-chain-enhancer of activated β cells (NF-κB), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) levels were investigated. A total of 56 patients with first occurrence of cerebral aneurysm rupture were enrolled from June 2015 to June 2016. These patients were divided into control (25 patients) and observation groups (31 patients) according to treatment received...
October 2017: Experimental and Therapeutic Medicine
Matthew Dale, Matthew P Fitzgerald, Zhibo Liu, Trevor Meisinger, Andrew Karpisek, Laura N Purcell, Jeffrey S Carson, Paul Harding, Haili Lang, Panagiotis Koutakis, Rishi Batra, Constance J Mietus, George Casale, Iraklis Pipinos, B Timothy Baxter, Wanfen Xiong
Thoracic aortic aneurysm and dissection are life-threatening complications of Marfan syndrome (MFS). Studies of human and mouse aortic samples from late stage MFS demonstrate increased TGF-β activation/signaling and diffuse matrix changes. However, the role of the aortic smooth muscle cell (SMC) phenotype in early aneurysm formation in MFS has yet to be fully elucidated. As our objective, we investigated whether an altered aortic SMC phenotype plays a role in aneurysm formation in MFS. We describe previously unrecognized concordant findings in the aortas of a murine model of MFS, mgR, during a critical and dynamic phase of early development...
2017: PloS One
Michihide Nishihara, Hiroki Aoki, Satoko Ohno, Aya Furusho, Saki Hirakata, Norifumi Nishida, Sohei Ito, Makiko Hayashi, Tsutomu Imaizumi, Yoshihiro Fukumoto
Although the pathogenesis of abdominal aortic aneurysm (AAA) remains unclear, evidence is accumulating to support a central role for inflammation. Inflammatory responses are coordinated by various soluble cytokines of which IL-6 is one of the major proinflammatory cytokines. In this study we examined the role of IL-6 in the pathogenesis of experimental AAA induced by a periaortic exposure to CaCl2 in mice. We now report that the administration of MR16-1, a neutralizing monoclonal antibody specific for the mouse IL-6 receptor, mildly suppressed the development of AAA...
2017: PloS One
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