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https://www.readbyqxmd.com/read/29310800/matrix-metalloproteinases-vascular-remodeling-and-vascular-disease
#1
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
https://www.readbyqxmd.com/read/29296615/minocycline-protects-against-delayed-cerebral-ischemia-after-subarachnoid-hemorrhage-via-matrix-metalloproteinase-9-inhibition
#2
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
https://www.readbyqxmd.com/read/29290496/fucoidan-attenuates-angiotensin-ii-induced-abdominal-aortic-aneurysms-through-the-inhibition-of-c-jun-n-terminal-kinase-and-nuclear-factor-%C3%AE%C2%BAb-activation
#3
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
https://www.readbyqxmd.com/read/29246325/ap-1-oligodeoxynucleotides-reduce-aortic-elastolysis-in-a-murine-model-of-marfan-syndrome
#4
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
https://www.readbyqxmd.com/read/29229950/aneurysm-severity-is-increased-by-combined-mmp-7-deletion-and-n-cadherin-mimetic-ec4-fc-over-expression
#5
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
https://www.readbyqxmd.com/read/29217508/il-1%C3%AE-interleukin-1%C3%AE-and-tnf-%C3%AE-tumor-necrosis-factor-%C3%AE-impact-abdominal-aortic-aneurysm-formation-by-differential-effects-on-macrophage-polarization
#6
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...
December 7, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29210916/acute-inflammatory-responses-to-exercise-in-patients-with-abdominal-aortic-aneurysm
#7
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
https://www.readbyqxmd.com/read/29131276/the-expression-of-mmp-7-in-serum-and-aneurysm-tissues-of-patients-with-abdominal-aortic-aneurysm-associated-with-hypertension-and-the-clinical-efficacy-of-endovascular-exclusion
#8
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
https://www.readbyqxmd.com/read/29073282/cardiovascular-phenotype-in-smad3-deficient-mice-with-renovascular-hypertension
#9
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
https://www.readbyqxmd.com/read/29061718/inhibition-of-aneurysm-progression-by-direct-renin-inhibition-in-a-rabbit-model
#10
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...
October 23, 2017: Hypertension
https://www.readbyqxmd.com/read/29042973/the-efficacy-of-microsurgery-in-the-treatment-of-cerebral-aneurysm-rupture-and-its-effect-on-nf-%C3%AE%C2%BAb-mcp-1-and-mmp-9
#11
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
https://www.readbyqxmd.com/read/29040313/premature-aortic-smooth-muscle-cell-differentiation-contributes-to-matrix-dysregulation-in-marfan-syndrome
#12
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
https://www.readbyqxmd.com/read/28982132/the-role-of-il-6-in-pathogenesis-of-abdominal-aortic-aneurysm-in-mice
#13
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
https://www.readbyqxmd.com/read/28978552/tryptophan-derived-3-hydroxyanthranilic-acid-contributes-to-angiotensin-ii-induced-abdominal-aortic-aneurysm-formation-in-mice-in-vivo
#14
Qiongxin Wang, Ye Ding, Ping Song, Huaiping Zhu, Imoh S Okon, Nan-Yang Ding, Houzao Chen, Depei Liu, Ming-Hui Zou
Background -Abnormal amino acid metabolism is associated with vascular disease. However, the causative link between dysregulated tryptophan metabolism and abdominal aortic aneurysm (AAA) is unknown. Methods -Indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting enzyme in the kynurenine pathway of tryptophan metabolism. Mice with deficiencies in both apolipoprotein e (Apoe) and IDO (Apoe(-/-)/IDO(-/-)) were generated by cross-breeding IDO(-/-) mice with Apoe(-/-) mice. Results -The acute infusion of angiotensin II (AngII) markedly increased the incidence of AAA in Apoe(-/-) mice, but not in Apoe(-/-)/IDO(-/-) mice, which presented decreased elastic lamina degradation and aortic expansion...
October 4, 2017: Circulation
https://www.readbyqxmd.com/read/28971841/role-of-myeloperoxidase-in-abdominal-aortic-aneurysm-formation-mitigation-by-taurine
#15
Ha Won Kim, Andra L Blomkalns, Mourad Ogbi, Manesh Thomas, Daniel Gavrila, Bonnie S Neltner, Lisa A Cassis, Robert W Thompson, Robert M Weiss, Paul D Lindower, Victor M Blanco, Michael L McCormick, Alan Daugherty, Xiaoming Fu, Stanley L Hazen, Brian K Stansfield, Yuqing Huo, David J Fulton, Tapan Chatterjee, Neal L Weintraub
Oxidative stress plays a fundamental role in abdominal aortic aneurysm (AAA) formation. Activated polymorphonuclear leukocytes (or neutrophils) are associated with AAA and express myeloperoxidase (MPO), which promotes inflammation, matrix degradation, and other pathological features of AAA, including enhanced oxidative stress through generation of reactive oxygen species. Both plasma and aortic MPO levels are elevated in patients with AAA, but the role of MPO in AAA pathogenesis has, heretofore, never been investigated...
December 1, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28950811/osteoclastogenesis-in-abdominal-aortic-aneurysms-a-new-therapeutic-target
#16
Alexander D Leung, Dai Yamanouchi
Abdominal aortic aneurysms (AAA) are a major cause of death. Currently, the mainstay of treatment for AAA is surgical repair and there are no FDA approved medical therapies for AAA. Much research is in progress to discover new medical therapies for AAA. The pathophysiology of AAA is understood to be a complex interplay of inflammatory and proteolytic processes that degenerate the aneurysm wall. Arterial calcification, which is observed in AAA but to a lesser extent than in arterial occlusive disease, occurs in a highly regulated manner in a similar process as mineral deposition in bone...
September 25, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28927932/chitosan-doxycycline-hydrogel-an-mmp-inhibitor-sclerosing-embolizing-agent-as-a-new-approach-to-endoleak-prevention-and-treatment-after-endovascular-aneurysm-repair
#17
Fatemeh Zehtabi, Pompilia Ispas-Szabo, Djahida Djerir, Lojan Sivakumaran, Borhane Annabi, Gilles Soulez, Mircea Alexandru Mateescu, Sophie Lerouge
The success of endovascular repair of abdominal aortic aneurysms remains limited due to the development of endoleaks. Sac embolization has been proposed to manage endoleaks, but current embolizing materials are associated with frequent recurrence. An injectable agent that combines vascular occlusion and sclerosing properties has demonstrated promise for the treatment of endoleaks. Moreover, the inhibition of aneurysmal wall degradation via matrix metalloproteinases (MMPs) may further prevent aneurysm progression...
December 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28875468/multifunctional-jnk-inhibiting-nanotherapeutics-for-augmented-elastic-matrix-regenerative-repair-in-aortic-aneurysms
#18
Andrew Camardo, Dhruv Seshadri, Tom Broekelmann, Robert Mecham, Anand Ramamurthi
Growth of abdominal aortic aneurysms (AAA), localized aortal wall expansions, is driven by the disruption and subsequent loss of aortal wall elastic fibers by matrix metalloproteases (MMPs). Since elastic fibers do not naturally regenerate or repair, arresting/reversing AAA growth has not been possible. Previously, we showed utility of doxycycline (DOX), an MMP inhibitor drug, to stimulate elastic matrix neoassembly and crosslinking at low microgram per milliliter doses in addition to inhibiting MMPs. We currently show in aneurysmal smooth muscle cell (SMC) cultures that effects of exogenous DOX in this dose range are linked to its upregulation of transforming growth factor beta (TGF-β1) via its inhibition of the regulatory protein c-Jun-N-terminal kinase 2 (JNK 2)...
September 5, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28839206/grape-seed-polyphenols-play-a-protective-role-in-elastase-induced-abdominal-aortic-aneurysm-in-mice
#19
Chao Wang, Yunxia Wang, Maomao Yu, Cong Chen, Lu Xu, Yini Cao, Rong Qi
Abdominal aortic aneurysm (AAA) is a kind of disease characterized by aortic dilation, whose pathogenesis is linked to inflammation. This study aimed to determine whether grape-seed polyphenols (GSP) has anti-AAA effects and what mechanism is involved, thus to find a way to prevent occurrence and inhibit expansion of small AAA. In our study, AAA was induced by incubating the abdominal aorta of the mice with elastase, and GSP was administrated to the mice by gavage at different doses beginning on the day of the AAA inducement...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28735290/membrane-tethered-metalloproteinase-expressed-by-vascular-smooth-muscle-cells-limits-the-progression-of-proliferative-atherosclerotic-lesions
#20
Richard H Barnes, Takeshi Akama, Miina K Öhman, Moon-Sook Woo, Julian Bahr, Stephen J Weiss, Daniel T Eitzman, Tae-Hwa Chun
BACKGROUND: The MMP (matrix metalloproteinase) family plays diverse and critical roles in directing vascular wall remodeling in atherosclerosis. Unlike secreted-type MMPs, a member of the membrane-type MMP family, MT1-MMP (membrane-type 1 MMP; MMP14), mediates pericellular extracellular matrix degradation that is indispensable for maintaining physiological extracellular matrix homeostasis. However, given the premature mortality exhibited by MT1-MMP-null mice, the potential role of the proteinase in atherogenesis remains elusive...
July 22, 2017: Journal of the American Heart Association
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