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Atherosclerosis MMPs

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https://www.readbyqxmd.com/read/29660282/design-radio-synthesis-in-vitro-and-in-vivo-evaluation-of-highly-selective-and-potent-matrix-metalloproteinase-mmp-12-inhibitors-as-radiotracers-for-positron-emission-tomography
#1
Viktoria Butsch, Frederik Börgel, Fabian Galla, Katrin Schwegmann, Sven Hermann, Michael Schäfers, Burkhard Riemann, Bernhard Wünsch, Stefan Wagner
Dysregulated levels of activated matrix metalloproteinases (MMPs) are linked to different pathologies such as cancer, atherosclerosis, neuroinflammation and arthritis. Therefore imaging of MMPs with positron emission tomography (PET) represents a powerful tool for the diagnosis of MMP associated diseases. Moreover, to distinguish between the distinct functions and roles of individual MMPs in particular pathophysiological processes their specific imaging must be realized with radiolabeled tracers e.g. fluorine-18 labeled MMP inhibitors (MMPIs)...
April 16, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29628981/troglitazone-inhibits-matrix-metalloproteinase-9-expression-and-invasion-of-breast-cancer-cell-through-a-peroxisome-proliferator-activated-receptor-%C3%AE-dependent-mechanism
#2
On-Yu Hong, Hyun Jo Youn, Hye-Yeon Jang, Sung Hoo Jung, Eun-Mi Noh, Hee Suk Chae, Young-Ju Jeong, Won Kim, Cheorl-Ho Kim, Jong-Suk Kim
Purpose: Peroxisome proliferator-activated receptor γ (PPARγ) is involved in the pathology of numerous diseases including atherosclerosis, diabetes, obesity, and cancer. Matrix metalloproteinases (MMPs) play a significant role in tissue remodeling related to various processes such as morphogenesis, angiogenesis, tissue repair, invasion, and metastasis. We investigated the effects of PPARγ on MMP expression and invasion in breast cancer cells. Methods: MCF-7 cells were cultured and then cell viability was monitored in an MTT assay...
March 2018: Journal of Breast Cancer
https://www.readbyqxmd.com/read/29579712/ginkgetin-ameliorates-experimental-atherosclerosis-in-rats
#3
Naqi Lian, Jing Tong, Wenwen Li, Jingzhen Wu, Yu Li
Atherosclerosis is a common disease seriously detrimental to human health. Natural products are important sources of therapeutic candidates for atherosclerosis. We here evaluated the effects of ginkgetin on experimental atherosclerosis in rats and explored the underlying mechanisms. Atherosclerosis was induced by high-fat diet for 12 weeks combined with single intraperitoneal injection of vitamin D3 in rats. The atherosclerotic rats were then treated with ginkgetin at 25, 50 and 100 mg/kg/d or simvastatin at 2 mg/kg/d for 8 weeks...
March 23, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29432898/acarbose-inhibits-the-proliferation-and-migration-of-vascular-smooth-muscle-cells-via-targeting-ras-signaling
#4
Meng-Hsun Yu, Ming-Cheng Lin, Chien-Ning Huang, Kuei-Chuan Chan, Chau-Jong Wang
Atherosclerosis involves the proliferation and migration of vascular smooth muscle cells (VSMCs). The migration of VSMCs from the media into the intima and their subsequent proliferation are important processes in neointima formation in atherosclerosis and restenosis after percutaneous coronary interventions. Acarbose, an alpha-glucosidase inhibitor, has been demonstrated to not affect serum levels of glucose and decrease the progression of intima-media thickening in rabbits fed with a high cholesterol diet (HCD)...
February 9, 2018: Vascular Pharmacology
https://www.readbyqxmd.com/read/29423648/an-integrated-structure-and-pharmacophore-based-mmp-12-virtual-screening
#5
Mohammad Ramezani, Jamal Shamsara
MMP-12 belongs to a large family of proteases called matrix metalloproteinases (MMPs) that degrades elastin. The main pathologic role of MMP-12 overexpression was suggested to be associated with pathogenesis mechanism of inflammatory respiratory diseases and atherosclerosis. An integrated ligand- and structure-based virtual screening was employed in hope of finding inhibitors with new scaffolds and selectivity for MMP-12. Seven compounds among 18 experimentally tested compounds had a measurable effect on the inhibition of MMP-12 enzyme...
February 8, 2018: Molecular Diversity
https://www.readbyqxmd.com/read/29414148/exenatide-modulates-metalloproteinase-expression-in-human-cardiac-smooth-muscle-cells-via-the-inhibition-of-akt-signaling-pathway
#6
Enrique Gallego-Colon, Agnieszka Klych-Ratuszny, Agnieszka Kosowska, Wojciech Garczorz, Mohammad Reza F Aghdam, Michal Wozniak, Tomasz Francuz
BACKGROUND: Incretin analogue drugs, a FDA-approved treatment in diabetes, has been tested for its therapeutic properties as modulators of atherosclerosis. We investigated the effects of incretin drugs on the modulation of gene expression and protein levels of matrix metalloproteinases (MMPs) as well as their inhibitors - tissue inhibitors of metalloproteinases (TIMPs) in coronary artery smooth muscle cells (hCASMC) in the context of atherosclerotic plaque formation and inflammation. METHODS: TNFα-stimulated hCASMC were treated with Glucagon-like Peptide 1 (GLP-1) (10 nM and 100 nM) and Exendin-4 (1 nM and 10 nM)...
October 4, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29326312/foxo3a-forkhead-transcription-factor-o-subfamily-member-3a-links-vascular-smooth-muscle-cell-apoptosis-matrix-breakdown-atherosclerosis-and-vascular-remodeling-through-a-novel-pathway-involving-mmp13-matrix-metalloproteinase-13
#7
Haixiang Yu, Adam Fellows, Kirsty Foote, Zhaoqing Yang, Nichola Figg, Trevor Littlewood, Martin Bennett
OBJECTIVE: Vascular smooth muscle cell (VSMC) apoptosis accelerates atherosclerosis and promotes breakdown of the extracellular matrix, but the mechanistic links between these 2 processes are unknown. The forkhead protein FOXO3a (forkhead transcription factor O subfamily member 3a) is activated in human atherosclerosis and induces a range of proapoptotic and other transcriptional targets. We, therefore, determined the mechanisms and consequences of FOXO3a activation in atherosclerosis and arterial remodeling after injury...
March 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29310800/matrix-metalloproteinases-vascular-remodeling-and-vascular-disease
#8
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/29283509/exenatide-exhibits-anti-inflammatory-properties-and-modulates-endothelial-response-to-tumor-necrosis-factor-%C3%AE-mediated-activation
#9
Wojciech Garczorz, Enrique Gallego-Colon, Agnieszka Kosowska, Agnieszka Kłych-Ratuszny, Michał Woźniak, Wiesław Marcol, K J Niesner, Tomasz Francuz
INTRODUCTION: Cardiovascular disease is the main cause of mortality and morbidity in the industrialized world. Incretin-mimetic compounds such as exenatide are currently used in the treatment of type 2 diabetes. AIMS: We investigated the effects of incretin drugs on apoptosis, adhesion molecule expression, and concentration of extracellular matrix (ECM) metalloproteinases under inflammatory conditions within the context of atherosclerotic plaque formation of both human coronary artery endothelial cells (hCAECs) and human aortic endothelial cells (hAoECs)...
April 2018: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/29163211/oxidative-stress-in-the-local-and-systemic-events-of-apical-periodontitis
#10
REVIEW
Patricia Hernández-Ríos, Pirkko J Pussinen, Rolando Vernal, Marcela Hernández
Oxidative stress is involved in the pathogenesis of a variety of inflammatory disorders. Apical periodontitis (AP) usually results in the formation of an osteolytic apical lesion (AL) caused by the immune response to endodontic infection. Reactive oxygen species (ROS) produced by phagocytic cells in response to bacterial challenge represent an important host defense mechanism, but disturbed redox balance results in tissue injury. This mini review focuses on the role of oxidative stress in the local and associated systemic events in chronic apical periodontitis...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29016728/augmented-th17-differentiation-in-trim21-deficiency-promotes-a-stable-phenotype-of-atherosclerotic-plaques-with-high-collagen-content
#11
Susanna Brauner, Xintong Jiang, Gudny Ella Thorlacius, Anna M Lundberg, Therese Östberg, Zhong-Qun Yan, Vijay K Kuchroo, Göran K Hansson, Marie Wahren-Herlenius
Aims: Patients with hyperlipidemia are at risk of atherosclerosis, but not all develop cardiovascular disease, highlighting the importance of other risk factors such as inflammation. Both the innate and adaptive arms of the immune system have been suggested in the initiation and propagation of plaque formation. Tri-partite motif (TRIM) 21 is a regulator of tissue inflammation and pro-inflammatory cytokine production, and has been implicated in chronic inflammatory disease. Here, we investigate a potential role for TRIM21 in coronary artery disease...
January 1, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/28953404/targeted-polypharmacology-discovery-of-a-highly-potent-non-hydroxamate-dual-matrix-metalloproteinase-mmp-10-13-inhibitor
#12
Nicole Senn, Michael Ott, Jan Lanz, Rainer Riedl
Matrix metalloproteinases (MMPs) play a key role in many diseases like cancer, atherosclerosis or arthritis. Interest in MMP inhibition has been revitalized very recently as the knowledge on the underlying network of biological pathways is steadily growing. On the basis of this new insight into the relevance of MMP-10 and MMP-13 within the MMP network and the ban of hydroxamate inhibitors from clinical development, the discovery of non-hydroxamate multitarget drugs against specific MMPs is of foremost interest...
October 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28893577/metalloproteinases-in-atherosclerosis
#13
Jason L Johnson
Atherosclerosis underlies most cardiovascular diseases, and is accepted as a primary cause of mortality worldwide. Proteases have been implicated in the development and progression of atherosclerosis, due to their ability to provoke focal destruction of the vascular extracellular matrix. Members of the metalloproteinase family, especially matrix metalloproteinases (MMPs), and their endogenous tissue inhibitors (TIMPs) have been suggested to perform complex dual roles during late-stage progression and rupture of atherosclerotic plaques...
September 9, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28746820/the-role-of-damage-and-pathogen-associated-molecular-patterns-in-inflammation-mediated-vulnerability-of-atherosclerotic-plaques
#14
Vikrant Rai, Devendra K Agrawal
Atherosclerosis is a chronic inflammatory disease resulting in the formation of the atherosclerotic plaque. Plaque formation starts with the inflammation in fatty streaks and progresses through atheroma, atheromatous plaque, and fibroatheroma leading to development of stable plaque. Hypercholesterolemia, dyslipidemia, and hyperglycemia are the risk factors for atherosclerosis. Inflammation, infection with viruses and bacteria, and dysregulation in the endothelial and vascular smooth muscle cells leads to advanced plaque formation...
October 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28735290/membrane-tethered-metalloproteinase-expressed-by-vascular-smooth-muscle-cells-limits-the-progression-of-proliferative-atherosclerotic-lesions
#15
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
https://www.readbyqxmd.com/read/28734077/integrative-studies-implicate-matrix-metalloproteinase-12-as-a-culprit-gene-for-large-artery-atherosclerotic-stroke
#16
H Mahdessian, L Perisic Matic, M Lengquist, K Gertow, B Sennblad, D Baldassarre, F Veglia, S E Humphries, R Rauramaa, U de Faire, A J Smit, P Giral, S Kurl, E Mannarino, E Tremoli, A Hamsten, P Eriksson, U Hedin, A Mälarstig
BACKGROUND: Ischaemic stroke and coronary heart disease are important contributors to the global disease burden and share atherosclerosis as the main underlying cause. Recent evidence from a genome-wide association study (GWAS) suggested that single nucleotide polymorphisms (SNP) near the MMP12 gene at chromosome 11q22.3 were associated with large-vessel ischaemic stroke. Here, we evaluated and extended these results by examining the relationship between MMP12 and atherosclerosis in clinical and experimental studies...
November 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28687781/p2x7-receptor-antagonism-modulates-il-1%C3%AE-and-mmp9-in-human-atherosclerotic-vessels
#17
Maria Lombardi, Maria Elena Mantione, Domenico Baccellieri, David Ferrara, Renata Castellano, Roberto Chiesa, Ottavio Alfieri, Chiara Foglieni
In atherosclerosis, matrix metallopeptidases (MMPs) contribute to plaque rupture through weakening of the fibrous cap. Pleiotropic P2X purinoceptor 7 (P2X7), expressed in the carotid plaque (PL), is involved in interleukin 1 beta (IL-1β) release that may influence MMP9 generation, thus their possible modulation through acting on P2X7 was investigated. P2X7-related machinery was characterized and the effects of P2X7 antagonists (A740003, KN62) and MMPs inhibitors (Batimastat, Ro28-2653) were studied in ex-vivo tissue cultures of human PL's vs...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28662828/matrix-metalloproteinase-inhibitors-as-investigational-and-therapeutic-tools-in-unrestrained-tissue-remodeling-and-pathological-disorders
#18
Jie Liu, Raouf A Khalil
Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes that degrade various proteins in the extracellular matrix (ECM). MMPs may also regulate the activity of membrane receptors and postreceptor signaling mechanisms and thereby affect cell function. The MMP family includes collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs, and other MMPs. Inactive proMMPs are cleaved by other MMPs or proteases into active MMPs, which interact with various protein substrates in ECM and cell surface...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28618427/matrix-metalloproteases-in-arterial-hypertension-and-their-trend-after-antihypertensive-treatment
#19
Eugenia Hopps, Rosalia Lo Presti, Gregorio Caimi
BACKGROUND/AIMS: Arterial hypertension is characterized by vascular remodelling, atherosclerosis and cardiovascular complications. Matrix metalloproteases (MPPs) are endopeptidases produced by all the cells present in the vascular wall and are involved in the regulation of the extracellular matrix protein turnover. MMPs contribute to blood vessel formation, remodelling, angiogenesis; whereas an altered expression or activity of MMPs or their tissue inhibitors (TIMPs) results correlated with the development and progression of cardiovascular complications...
2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/28506859/the-obstructed-bladder-expression-of-collagen-matrix-metalloproteinases-muscarinic-receptors-and-angiogenic-and-neurotrophic-factors-in-patients-with-benign-prostatic-hyperplasia
#20
João Arthur Brunhara Alves Barbosa, Sabrina T Reis, Marco Nunes, Yuri A Ferreira, Katia R Leite, William C Nahas, Miguel Srougi, Alberto A Antunes
OBJECTIVE: To evaluate the gene expression of collagen, matrix metalloproteinases (MMPs) and inhibitors, cholinergic muscarinic receptors (CHRMs), and angiogenic and nerve growth factors (NGFs) in the bladder of patients with bladder outlet obstruction caused by benign prostatic hyperplasia (BPH). METHODS: We analyzed bladder specimens from 43 patients with obstructive BPH undergoing transurethral resection of the prostate as compared to 10 age-matched controls with an International Prostatic Symptom Score of <8 and a prostate volume of <30 g...
August 2017: Urology
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