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https://www.readbyqxmd.com/read/28433630/loss-of-murc-cavin-4-induces-jnk-and-mmp-9-activity-enhancement-in-vascular-smooth-muscle-cells-and-exacerbates-abdominal-aortic-aneurysm
#1
Kotaro Miyagawa, Takehiro Ogata, Tomomi Ueyama, Takeru Kasahara, Naohiko Nakanishi, Daisuke Naito, Takuya Taniguchi, Tetsuro Hamaoka, Naoki Maruyama, Masahiro Nishi, Taizo Kimura, Hiroyuki Yamada, Hiroki Aoki, Satoaki Matoba
Abdominal aortic aneurysm (AAA) is relatively common in elderly patients with atherosclerosis. MURC (muscle-restricted coiled-coil protein)/Cavin-4 modulating the caveolae function of muscle cells is expressed in cardiomyocytes, skeletal muscle cells and smooth muscle cells. Here, we show a novel functional role of MURC/Cavin-4 in vascular smooth muscle cells (VSMCs) and AAA development. Both wild-type (WT) and MURC/Cavin-4 knockout (MURC(-/-)) mice subjected to periaortic application of CaCl2 developed AAAs...
April 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28420827/relaxin-and-matrix-metalloproteinase-9-in-angiotensin-ii-induced-abdominal-aortic-aneurysms
#2
Deborah A Howatt, Maya Dajee, Xiaojie Xie, Jessica Moorleghen, Debra L Rateri, Anju Balakrishnan, Valdeci Da Cunha, Douglas G Johns, David E Gutstein, Alan Daugherty, Hong Lu
BACKGROUND: This study determined whether relaxin or matrix metalloproteinase (MMP)-9 influences angiotensin II (AngII)-induced abdominal aortic aneurysms (AAA).Methods and Results:Male C57BL/6 or apolipoprotein E(-/-)mice were infused with AngII with or without relaxin. Relaxin did not influence AngII-induced AAA in either mouse strain. Infusion of AngII reduced, but relaxin increased, MMP-9 mRNA in macrophages. We then determined the effects of MMP-9 deficiency on AAA in apolipoprotein E(-/-)mice...
April 18, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28413030/the-role-matrix-metalloproteinases-in-the-production-of-aortic-aneurysm
#3
Simon W Rabkin
Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of aortic aneurysm because the histology of thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) is characterized by the loss of smooth muscle cells in the aortic media and the destruction of extracellular matrix (ECM). Furthermore, AAA have evidence of inflammation and the cellular elements involved in inflammation such as macrophages can produce and/or activate MMPs This chapter focuses on human aortic aneurysm that are not due to specific known genetic causes because this type of aneurysm is the more common type...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28413027/matrix-metalloproteinases-and-platelet-function
#4
Paolo Gresele, Emanuela Falcinelli, Manuela Sebastiano, Stefania Momi
Platelets contain and release several matrix metalloproteinases (MMPs) and their tissue inhibitors of matrix metalloproteinases (TIMPs), including MMP-1, -2, -3, -9, and -14 and TIMP-1, -2, and -4. Although devoid of a nucleus, platelets also synthesize TIMP-2 upon activation. Platelet-released MMPs/TIMPs, as well as MMPs generated by other cells within the cardiovascular system, modulate platelet function in health and disease. In particular, a normal hemostatic platelet response to vessel wall injury may be transformed into pathologic thrombus formation by the release from platelets and/or by the local generation of some MMPs...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28413025/biochemical-and-biological-attributes-of-matrix-metalloproteinases
#5
Ning Cui, Min Hu, Raouf A Khalil
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are involved in the degradation of 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...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28364044/high-serum-thrombospondin-1-concentration-is-associated-with-slower-abdominal-aortic-aneurysm-growth-and-deficiency-promotes-angiotensin-ii-induced-aneurysm-in-mice
#6
Smriti M Krishna, Saiwang Seto, Roby Jose, Jiaze Li, Joseph V Moxon, Paula Clancy, David J Crossman, Paul E Norman, Theophilus I Emeto, Jonathan Golledge
Abdominal aortic aneurysm (AAA) is a common age-related vascular disease characterized by progressive weakening and dilatation of the aortic wall. Thrombospondin-1 (TSP-1; gene Thbs1) is a member of the matricellular protein family important in the control of extracellular matrix remodeling. In this study, the association of serum TSP-1 concentration with AAA progression was assessed in 276 men that underwent repeat ultrasound for a median 5.5 years. AAA growth was negatively correlated with serum TSP-1 concentration ( Spearman's rho (-)0...
March 31, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28360209/preclinical-evaluation-of-rym1-a-novel-mmp-targeted-tracer-for-imaging-aneurysm
#7
Jakub Toczek, Yunpeng Ye, Kiran Gona, Hye-Yeong Kim, Jinah Han, Mahmoud Razavian, Reza Golestani, Jiasheng Zhang, Terence Wu, Jae-Joon Jung, Mehran Sadeghi
Matrix metalloproteinases (MMPs) play a key role in abdominal aortic aneurysm (AAA) development. Accordingly, MMP-targeted imaging provides important information regarding vessel wall biology in the course of aneurysm development. Given the small size of the vessel wall and its proximity with blood, molecular imaging of aneurysm optimally requires highly sensitive tracers with rapid blood clearance. To this end, we developed a novel hydrosoluble zwitterionic MMP inhibitor, RYM, based on which a pan-MMP tracer, RYM1, was designed...
March 30, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28296545/the-effects-of-nicotine-administration-on-the-pathophysiology-of-rat-aortic-wall
#8
H Kugo, N Zaima, H Tanaka, T Urano, N Unno, T Moriyama
Abdominal aortic aneurysm (AAA) is the progressive dilation of the abdominal aorta. Nicotine is reported to be associated with the development and rupture of AAA, but the pathological effects of nicotine on normal rat aorta have not been determined. We investigated pathological changes in the aortic wall of rats caused by the administration of nicotine. Nicotine administration weakened the vascular wall, increased gelatinolytic activity and promoted the destruction of elastin and collagen in the rat abdominal aorta...
2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/28288890/abdominal-aortic-aneurysm-associated-microrna-516a-5p-regulates-expressions-of-methylenetetrahydrofolate-reductase-matrix-metalloproteinase-2-and-tissue-inhibitor-of-matrix-metalloproteinase-1-in-human-abdominal-aortic-vascular-smooth-muscle-cells
#9
Crystal Yin Tung Chan, Bernice Lai Yee Cheuk, Stephen Wing Keung Cheng
BACKGROUND: MicroRNAs (miRNAs or miRs) have been highlighted to be involved in abdominal aortic aneurysm (AAA) with the emergence of recent miRNA microarray profiling studies. miR-516a-5p has been shown to be significantly overexpressed in vascular smooth muscle cells (VSMCs) from human AAA tissues from our previous microarray study, suggesting its crucial association with AAA. In addition, further bioinformatics analysis predicted methylenetetrahydrofolate reductase (MTHFR), which regulates homocysteine (Hcy) metabolism and is proposed to be a risk gene for AAA formation and to be the downregulation target of miR-516a-5p...
March 10, 2017: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/28220880/parenteral-administration-of-factor-xa-iia-inhibitors-limits-experimental-aortic-aneurysm-and-atherosclerosis
#10
Corey S Moran, Sai-Wang Seto, Smriti M Krishna, Surabhi Sharma, Roby J Jose, Erik Biros, Yutang Wang, Susan K Morton, Jonathan Golledge
Intraluminal thrombus is a consistent feature of human abdominal aortic aneurysm (AAA). Coagulation factor Xa (FXa) catalyses FII to thrombin (FIIa). We examined the effect of FXa/FIIa inhibition on experimental aortic aneurysm in apolipoprotein E-deficient (ApoE(-/-)) mice infused with angiotensin II (AngII). The concentration of FXa within the supra-renal aorta (SRA) correlated positively with SRA diameter. Parenteral administration of enoxaparin (FXa/IIa inhibitor) and fondaparinux (FXa inhibitor) over 14 days reduced to severity of aortic aneurysm and atherosclerosis in AngII-infused ApoE(-/-) mice...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209269/association-of-matrix-metalloproteinase-levels-with-collagen-degradation-in-the-context-of-abdominal-aortic-aneurysm
#11
V Klaus, F Tanios-Schmies, C Reeps, M Trenner, E Matevossian, H-H Eckstein, J Pelisek
OBJECTIVE/BACKGROUND: Matrix metalloproteinases (MMPs) have already been identified as key players in the pathogenesis of abdominal aortic aneurysm (AAA). However, the current data remain inconclusive. In this study, the expression of MMPs at mRNA and protein levels were investigated in relation to the degradation of collagen I and collagen III. METHODS: Tissue samples were obtained from 40 patients with AAA undergoing open aortic repair, and from five healthy controls during kidney transplantation...
February 10, 2017: European Journal of Vascular and Endovascular Surgery
https://www.readbyqxmd.com/read/28195071/spatial-differences-of-matrix-metalloproteinase-2-and-matrix-metalloproteinase-9-within-abdominal-aortic-aneurysm-wall-and-intraluminal-thrombus
#12
A Siennicka, M Zuchowski, M Kaczmarczyk, M Cnotliwy, J S Clark, M Jastrzebska
Formation of an abdominal aortic aneurysm is a complex process involving aortic wall degradation. The matrix metalloproteinases (MMPs) mainly involved in this process are MMP-2 and MMP-9. Most aneurysms contain an intraluminal thrombus. It is suggested that the thrombus' thickness correlates with the risk of aneurysm rupture and may be a new prognostic factor. The purpose of the present study was to investigate enzyme protein levels in thick (A1) and thin (B1) segments of the thrombus and aneurysm wall sections A (adjacent to A1) and B (adjacent to B1)...
December 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28179203/involvement-of-matrix-metalloproteinases-in-chronic-q-fever
#13
Anne F M Jansen, Teske Schoffelen, Julien Textoris, Jean Louis Mege, Chantal P Bleeker-Rovers, Hendrik I J Roest, Peter C Wever, Leo A B Joosten, Mihai G Netea, Esther van de Vosse, Marcel van Deuren
OBJECTIVES: Chronic Q fever is a persistent infection with the intracellular Gram-negative bacterium Coxiella burnetii, which can lead to complications of infected aneurysms. Matrix metalloproteinases (MMPs) cleave extracellular matrix and are involved in infections as well as aneurysms. We aimed to study the role of MMPs in the pathogenesis of chronic Q fever. METHODS: We investigated gene expression of MMPs through microarray analysis and MMP production with enzyme-linked immunosorbent assay in C...
February 4, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28155626/serum-calprotectin-as-a-novel-biomarker-in-abdominal-aortic-aneurysm-pathogenesis-and-progression-preliminary-data-from-experimental-model-in-rats
#14
Demetrios Moris, Stamatios Theocharis, Spyridon Davakis, Nikolaos Patelis, Georgios Agrogiannis, Ioannis S Vlachos, Eleftherios Spartalis, Antonios Athanasiou, Chris Bakoyiannis, Despina N Perrea, Sotirios Georgopoulos
BACKGROUND: Abdominal aortic aneurysm (AAA) formation is associated with by inflammation and matrix degradation. This study tested the hypothesis that calprotectin, a novel biomarker for inflammation, as well as established biomarkers such as C-reactive protein (CRP) and matrix metalloproteinase-9 (MMP-9) could also be indicative inflammatory biomarkers during AAA pathogenesis and progression. We also evaluated the correlation of serum soluble Receptor for Advanced Glycation End Products (sRAGE) with AAA diameter and serum calprotectin levels...
February 2, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28142259/ace2-inhibits-angiotensin-ii-induced-abdominal-aortic-aneurysm-in-mice
#15
QingQing Hao, XueFei Dong, Xu Chen, Feng Yan, Xiaoyu Wang, Haishui Shi, Bo Dong
Recent study have demonstrated that ACE2 plays an important role in the pathogenesis of abdominal Aortic Aneurysm (AAA). But, little study was reported about the direct effect of ACE2 overexpression on the aneurysm. In this study, we hypothesize that overexpression of ACE2 may prevent the pathogenesis of aneurysm by decreasing RAS activation. Thirty-nine Mice were assigned to 3 groups randomly (n=13 in each group), ACE2 group, Ad.EGFP group and Control group. After 8-week treatment, abdominal aortas with AAA were obtained for HE staining, VVG, immunohistochemistry and Western blotting...
January 31, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28101179/study-of-the-functional-mechanisms-of-osteopontin-and-chemokine-like-factor-1-in-the-development-and-progression-of-abdominal-aortic-aneurysms-in-rats
#16
Jun Li, Xia Bao, Yongxin Li, Yuewei Wang, Zonggang Zhao, Xing Jin
The aim of the study was to investigate the functional mechanisms of osteopontin (Opn) and chemokine-like factor 1 (Cklf1) during the development and progression of abdominal aortic aneurysms (AAA) in rats. Healthy adult Sprague-Dawley rats (n=30) were randomly divided into the AAA, control and sham groups (10 rats/group) and experimental rat models of AAA were generated by enzyme perfusion in abdominal aorta for 30 min. The AAA formation was assessed by measuring the aortal diameter and hematoxylin and eosin staining as well as specific staining to detect the structural changes of the aorta and inflammatory cell infiltration...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28101173/particularly-interesting-cys-his-rich-protein-is-highly-expressed-in-human-intracranial-aneurysms-and-resists-aneurysmal-rupture
#17
Yu-Tao Peng, Xiang-En Shi, Zhi-Qiang Li, Xin He, Yu-Ming Sun
Particularly interesting Cys-His-rich protein (PINCH) has several biological functions in cancer development, invasion and metastasis in malignant cells, and the expression of PINCH is upregulated in several cancer types, including breast cancer, gastric adenocarcinoma and rectal cancer. However, the contribution of PINCH to human cerebral aneurysms remains largely unknown. Therefore, the significance of PINCH expression in cerebral aneurysm growth and rupture was examined in the present study. The protein expression levels of alpha-smooth muscle actin, osteopontin (OPN), matrix metalloproteinase (MMP) 9 and PINCH were evaluated using immunohistochemistry and western blot analyses...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27923483/regulation-of-membrane-type-1-matrix-metalloproteinase-activity-and-intracellular-localization-in-clinical-thoracic-aortic-aneurysms
#18
John S Ikonomidis, Elizabeth K Nadeau, Adam W Akerman, Robert E Stroud, Rupak Mukherjee, Jeffrey A Jones
OBJECTIVE: Membrane type-1 matrix metalloproteinase (MT1-MMP) is elevated during thoracic aortic aneurysm (TAA) development in mouse models, and plays an important role in the activation of matrix metalloproteinase (MMP)-2 and the release of matrix- bound transforming growth factor-β. In this study, we tested the hypothesis that MT1-MMP is subject to protein kinase C (PKC)-mediated regulation, which alters intracellular trafficking and activity with TAAs. METHODS: Levels of MMP-2, native and phosphorylated MT1-MMP, and PKC-δ were measured in aortic tissue from patients with small TAAs (<5 cm; n = 8) and large TAAs (>6...
March 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/27917892/optical-imaging-of-mmp-12-active-form-in-inflammation-and-aneurysm
#19
Mahmoud Razavian, Thomas Bordenave, Dimitris Georgiadis, Fabrice Beau, Jiasheng Zhang, Reza Golestani, Jakub Toczek, Jae-Joon Jung, Yunpeng Ye, Hye-Yeong Kim, Jinah Han, Vincent Dive, Laurent Devel, Mehran M Sadeghi
Matrix metalloproteinase (MMP)-12 plays a key role in the development of aneurysm. Like other members of MMP family, MMP-12 is produced as a proenzyme, mainly by macrophages, and undergoes proteolytic activation to generate an active form. Accordingly, molecular imaging of the MMP-12 active form can inform of the pathogenic process in aneurysm. Here, we developed a novel family of fluorescent probes based on a selective MMP-12 inhibitor, RXP470.1 to target the active form of MMP-12. These probes were stable in complex media and retained the high affinity and selectivity of RXP470...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27884774/magnetically-responsive-multifunctional-drug-delivery-nanoparticles-for-elastic-matrix-regenerative-repair
#20
Balakrishnan Sivaraman, Ganesh Swaminathan, Lee Moore, Jonathan Fox, Dhruv Seshadri, Shataakshi Dahal, Ivan Stoilov, Maciej Zborowski, Robert Mecham, Anand Ramamurthi
Arresting or regressing growth of abdominal aortic aneurysms (AAAs), localized expansions of the abdominal aorta are contingent on inhibiting chronically overexpressed matrix metalloproteases (MMPs)-2 and -9 that disrupt elastic matrix within the aortic wall, concurrent with providing a stimulus to augmenting inherently poor auto-regeneration of these matrix structures. In a recent study we demonstrated that localized, controlled and sustained delivery of doxycycline (DOX; a tetracycline-based antibiotic) from poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs), enhances elastic matrix deposition and MMP-inhibition at a fraction of the therapeutically effective oral dose...
April 1, 2017: Acta Biomaterialia
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