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https://www.readbyqxmd.com/read/27923483/regulation-of-membrane-type-1-matrix-metalloproteinase-activity-and-intracellular-localization-in-clinical-thoracic-aortic-aneurysms
#1
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...
November 14, 2016: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/27917892/optical-imaging-of-mmp-12-active-form-in-inflammation-and-aneurysm
#2
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/esponsive-multifunctional-drug-delivery-nanoparticles-for-elastic-matrix-regenerative-repair
#3
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...
November 21, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27859600/differences-in-extracellular-matrix-proteins-between-friesian-horses-with-aortic-rupture-unaffected-friesians-and-warmblood-horses
#4
M Ploeg, A Gröne, C H A van de Lest, V Saey, L Duchateau, P Wolsein, K Chiers, R Ducatelle, P R van Weeren, M de Bruijn, C Delesalle
BACKGROUND: Aortic rupture is quite common in Friesian horses unlike in Warmblood horses and a hereditary trait is suspected in Friesians. The aortic connective tissue in affected Friesians shows histological changes such as medial necrosis, elastic fibre fragmentation, mucoid material accumulation and fibrosis with aberrant collagen morphology. However, ultrastructural examination of the collagen fibres of the mid-thoracic aorta was inconclusive when trying to further elucidate the pathogenesis of the disease...
November 16, 2016: Equine Veterinary Journal
https://www.readbyqxmd.com/read/27836291/the-megaaortic-syndrome-progression-of-ascending-aortic-aneurysm-or-a-disease-of-distinct-origin
#5
Ulrike Baranyi, Christian Stern, Birgitta Winter, Adrian Türkcan, Bernhard Scharinger, Marie-Elisabeth Stelzmüller, Thomas Aschacher, Martin Andreas, Marek Ehrlich, Günther Laufer, David Bernhard, Barbara Messner
BACKGROUND: Thoracic aortic aneurysm (TAA) is an often asymptomatic disease with fatal outcome, such as dissection or rupture. The megaaortic syndrome (MAS) is an extensive dilatation of the whole aorta with low incidence but high lethal outcome with unknown pathophysiology so far. METHODS AND RESULTS: We compared aortic tissue of patients with sporadic TAAs and MAS of the ascending aorta with non-aneurysmal control tissues. Specimens of MAS patients showed a significantly reduced thickness of the media but an increased thickness of the intima compared to control tissue and TAAs with moderate dilatation...
October 29, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27802285/mmp-2-isoforms-in-aortic-tissue-and-serum-of-patients-with-ascending-aortic-aneurysms-and-aortic-root-aneurysms
#6
Anke Tscheuschler, Philipp Meffert, Friedhelm Beyersdorf, Claudia Heilmann, Nadja Kocher, Xenia Uffelmann, Philipp Discher, Matthias Siepe, Fabian A Kari
OBJECTIVE: The need for biological markers of aortic wall stress and risk of rupture or dissection of ascending aortic aneurysms is obvious. To date, wall stress cannot be related to a certain biological marker. We analyzed aortic tissue and serum for the presence of different MMP-2 isoforms to find a connection between serum and tissue MMP-2 and to evaluate the potential of different MMP-2 isoforms as markers of high wall stress. METHODS: Serum and aortic tissue from n = 24 patients and serum from n = 19 healthy controls was analyzed by ELISA and gelatin zymography...
2016: PloS One
https://www.readbyqxmd.com/read/27800490/resistin-enhances-inflammatory-cytokine-production-in-coronary-artery-tissues-by-activating-the-nf-%C3%AE%C2%BAb-signaling
#7
Fang Gao, Feifei Si, Siqi Feng, Qijian Yi, Ruixi Liu
Purpose. Kawasaki disease (KD) is a systemic vasculitis and is a leading cause of coronary artery lesions (CALs) in childhood. Our previous study has shown higher levels of serum Resistin in KD patients with coronary aneurysm. This study aimed at examining the association of Resistin with inflammatory cytokine expression in mouse model of coronary arteritis and determining the potential mechanisms. Methods. C57BL/6 mice were injected with Lactobacillus cell wall extract (LCWE) to induce coronary arteritis. The relative levels of Resistin, TNF-α, IL-1β, and MMP-9 expression and inflammatory infiltrates in the coronary arteries were determined longitudinally by quantitative RT-PCR, ELISA, and histology...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27766267/advanced-glycation-end-products-and-its-soluble-receptors-in-the-pathogenesis-of-thoracic-aortic-aneurysm
#8
Kailash Prasad, Abdullah Sarkar, Mohammad A Zafar, Ahmed Shoker, Hamdi Ei Moselhi, Maryann Tranquilli, Bulat A Ziganshin, John A Elefteriades
BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of thoracic aortic aneurysms (TAAs). Cytokines [Interleukin (IL)-Iβ, IL-2, IL-6, and TNF-α)] increase the expression of MMP-2 and -3. Advanced glycation end products (AGEs) interact with cell receptors to increase the release of cytokines. Circulating soluble receptors for AGEs (sRAGE) and endogenous secretory RAGE (esRAGE) compete with membrane bound RAGE for binding with AGEs and reduce the production of cytokines...
February 2016: Aorta (Stamford, Conn.)
https://www.readbyqxmd.com/read/27764222/epa-prevents-the-development-of-abdominal-aortic-aneurysms-through-gpr-120-ffar-4
#9
Ryo Kamata, Batmunkh Bumdelger, Hiroki Kokubo, Masayuki Fujii, Koichi Yoshimura, Takafumi Ishida, Mari Ishida, Masao Yoshizumi
Abdominal aortic aneurysms (AAAs), which commonly occur among elderly individuals, are accompanied by a risk of rupture with a high mortality rate. Although eicosapentaenoic acid (EPA) has been reported to prevent AAA formation, the mechanism by which EPA works on vascular smooth muscle cells is unknown. This study aimed to investigate the mechanism by which orally-administered EPA prevents the formation of severe AAAs that develop in Osteoprotegerin (Opg) knockout (KO) mice. In the CaCl2-induced AAA model, EPA attenuated the enhanced progression of AAAs in Opg-KO mice, including the increase in aortic diameter with destruction of elastic fibers in the media...
2016: PloS One
https://www.readbyqxmd.com/read/27698934/reversal-of-vascular-calcification-and-aneurysms-in-a-rat-model-using-dual-targeted-therapy-with-edta-and-pgg-loaded-nanoparticles
#10
Nasim Nosoudi, Aniqa Chowdhury, Steven Siclari, Saketh Karamched, Vaideesh Parasaram, Joe Parrish, Patrick Gerard, Narendra Vyavahare
Degeneration of elastic lamina and vascular calcification are common features of vascular pathology such as aortic aneurysms. We tested whether dual therapy with targeted nanoparticles (NPs) can remove mineral deposits (by delivery of a chelating agent, ethylene diamine tetraacetic acid (EDTA)) and restore elastic lamina (by delivery of a polyphenol, pentagalloyl glucose (PGG)) to reverse moderate aneurysm development. EDTA followed by PGG NP delivery led to reduction in macrophage recruitment, matrix metalloproteinase (MMP) activity, elastin degradation and calcification in the aorta as compared to delivery of control blank NPs...
2016: Theranostics
https://www.readbyqxmd.com/read/27688602/sp600125-attenuates-nicotine-related-aortic-aneurysm-formation-by-inhibiting-matrix-metalloproteinase-production-and-cc-chemokine-mediated-macrophage-migration
#11
Zhen-Zhen Guo, Qun-An Cao, Zong-Zhuang Li, Li-Ping Liu, Zhi Zhang, Ya-Juan Zhu, Guang Chu, Qiu-Yan Dai
Nicotine, a major chemical component of cigarettes, plays a pivotal role in the development of abdominal aortic aneurysm (AAA). c-Jun N-terminal kinase (JNK) has been demonstrated to participate in elastase-induced AAA. This study aimed to elucidate whether the JNK inhibitor SP600125 can attenuate nicotine plus angiotensin II- (AngII-) induced AAA formation and to assess the underlying molecular mechanisms. SP600125 significantly attenuated nicotine plus AngII-induced AAA formation. The expression of matrix metalloproteinase- (MMP-) 2, MMP-9, monocyte chemoattractant protein- (MCP-) 1, and regulated-on-activation, normal T-cells expressed and secreted (RANTES) was significantly upregulated in aortic aneurysm lesions but inhibited by SP600125...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27663582/amelioration-of-salvianolic-acid-c-on-aortic-structure-in-apolipoprotein-e-deficient-mice-treated-with-angiotension-ii
#12
Peng Wu, Na Han, Haitao Yu, Linlin Wang, Xue Li, Zhihui Dong, Weiguo Fu, Hoichi Yorinaka, Kenka Cho, Wanying Wu, Xuan Liu, Min Yang, De-An Guo, Jun Yin, Baohong Jiang
AIMS: Aortic aneurysm is a disastrous vascular disease with high morbidity and mortality. Matrix metalloproteinases (MMPs), especially MMP-9, is implicated in the development of aortic aneurysm, but the effective MMP inhibitors are far from development. To develop new candidate compound for aortic aneurysm therapy, we evaluated the effects of salvianolic acid C (SalC) against the formation of aortic aneurysm. MATERIALS AND METHODS: Aortic aneurysm was induced by implantation of angiotension II (AngII) minipump in apolipoprotein E-deficient (ApoE(-/-)) mice...
September 20, 2016: Life Sciences
https://www.readbyqxmd.com/read/27659153/characterization-of-serum-matrix-metalloproteinase-2-9-levels-in-patients-with-ascending-aortic-aneurysms
#13
Philipp Meffert, Anke Tscheuschler, Friedhelm Beyersdorf, Claudia Heilmann, Nadja Kocher, Xenia Uffelmann, Philipp Discher, Bartosz Rylski, Matthias Siepe, Fabian A Kari
OBJECTIVES: The objectives of this study were to identify interrelations between matrix metalloproteinase-2 (MMP2)/MMP9 levels and clinical variables in patients with aortic root/ascending aortic aneurysms and to describe comorbidities as possible biasing factors in the widely discussed correlation of serum MMP levels and aortic diameter. METHODS: Serum MMP9 and MMP2 levels were quantified in 32 consecutive patients with ascending aortic and/or aortic root aneurysms (>45 mm) at the Heart Center University of Freiburg from May 2013 to January 2014...
September 22, 2016: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/27626316/heme-oxygenase-1-deficiency-exacerbates-angiotensin-ii-induced-aortic-aneurysm-in-mice
#14
Yen-Chun Ho, Meng-Ling Wu, Pei-Yu Gung, Chung-Huang Chen, Cheng-Chin Kuo, Shaw-Fang Yet
Abdominal aortic aneurysm (AAA) is a chronic but often fatal disease in elderly population. Heme oxygenase-1 (HO-1) is a stress response protein with antioxidative and anti-inflammatory properties. HO-1 has been shown to protect against atherogenesis and arterial intimal thickening. Emerging evidences suggest that AAA and arterial occlusive disease have distinct pathogenic mechanisms. Thus, in this study we investigated the role of HO-1 in angiotensin II-induced AAA formation in HO-1+/+apoE-/- and HO-1-/-apoE-/- mice...
September 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27624703/a-potential-role-for-glycated-cross-links-in-abdominal-aortic-aneurysm-disease
#15
Dave Koole, Joost A van Herwaarden, Casper G Schalkwijk, Floris P J G Lafeber, Aryan Vink, Mirjam B Smeets, Gerard Pasterkamp, Frans L Moll
BACKGROUND: Diabetes is a risk factor for atherosclerotic disease but negatively associated with the development and progression of abdominal aortic aneurysm (AAA). Advanced glycation end products (AGEs) are increased in diabetes and renders the vascular matrix more resistant to proteolysis. We assessed the concentration of AGEs in AAA biopsies obtained from diabetic and nondiabetic patients and hypothesized that (nonenzymatic) glycation of AAA tissue protects against proteolytic breakdown of collagen...
September 10, 2016: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/27619163/cytokine-amplification-and-macrophage-effector-functions-in-aortic-inflammation-and-abdominal-aortic-aneurysm-formation
#16
COMMENT
Talha Ijaz, Ronald G Tilton, Allan R Brasier
On April 29, 2015, Son and colleagues published an article entitled "Granulocyte macrophage colony-stimulating factor (GM-CSF) is required for aortic dissection/intramural haematoma" in Nature Communications. The authors observed that the heterozygous Kruppel-like transcription factor 6 (KLF6) deficiency or absence of myeloid-specific KLF6 led to upregulation of macrophage GM-CSF expression, promoted the development of aortic hematoma/dissection, and stimulated abdominal aortic aneurysm (AAA) formation when the vessel wall was subjected to an inflammatory stimulus...
August 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/27544600/inhibition-of-bet-bromodomain-attenuates-angiotensin-ii-induced-abdominal-aortic-aneurysm-in-apoe-mice
#17
Qiong Duan, Xiaoxiao Mao, Chaonan Liao, Haoyang Zhou, Zelin Sun, Xu Deng, Qiuning Hu, Jun Qi, Guogang Zhang, He Huang, Jorge Plutzky, Tianlun Yang
BACKGROUND: Excessive degradation of extracellular matrix by matrix metalloproteinases (MMP) is the major pathological feature of abdominal aortic aneurysm (AAA). Suppression of extracellular matrix degradation attenuates AAA initiation and progression in preclinical models. In the present study, we wanted to test the effect of JQ1, a small chemical molecule that selectively targets bromodomain and extra-terminal domain (BET), on AngII induced AAA formation in ApoE(-/-) mice. METHODS AND RESULTS: To study the role of BET bromodomain in AAA pathogenesis, male ApoE(-/-) mice were infused with angiotensin II (AngII, 1000ng/kg/min) for 21days and cotreated with JQ1 (50mg/kg daily) or vehicle control (DMSO)...
November 15, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27542007/systemic-delivery-of-nanoparticles-loaded-with-pentagalloyl-glucose-protects-elastic-lamina-and-prevents-abdominal-aortic-aneurysm-in-rats
#18
Nasim Nosoudi, Aniqa Chowdhury, Steven Siclari, Vaideesh Parasaram, Saketh Karamched, Naren Vyavahare
Degeneration of elastin plays a vital role in the pathology and progression of abdominal aortic aneurysm (AAA). Our previous study showed that pentagalloyl glucose (PGG), a core derivative of tannic acid, hinders the development of AAAs in a clinically relevant animal model when applied locally. In this study, we tested whether targeted nanoparticles (NPs) can deliver PGG to the site of an aneurysm and prevent aneurysmal growth by protecting elastin. PGG-loaded albumin NPs with a surface-conjugated elastin-specific antibody were prepared...
August 19, 2016: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/27533781/association-of-1166a-c-at1r-1562c-t-mmp-9-ace-i-d-and-ccr5%C3%AE-32-polymorphisms-with-abdominal-aortic-aneurysm-in-croatian-patients
#19
Andrea Crkvenac Gregorek, Kristina Crkvenac Gornik, Darija Stupin Polancec, Sanja Dabelic
AIM: The purpose of this case-control study was to assess the association of abdominal aortic aneurysm (AAA) in Croatian patients with four genetic polymorphisms: SNP 1166A>C in the angiotensin II type 1 receptor gene (AT1R); SNP -1562C>T in the matrix metalloproteinase-9 gene (MMP-9); the deletion of 32 bp in the chemokine receptor 5 gene (CCR5); and the insertion/deletion (I/D) of 287 bp in the angiotensin-converting enzyme gene (ACE). METHODS: Case-control study conducted with 117 patients with confirmed AAA (AAA(+)) and 117 control subjects (AAA(-))...
October 2016: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/27497884/silencing-of-hypoxia-inducible-factor-1%C3%AE-gene-attenuated-angiotensin-%C3%A2-induced-abdominal-aortic-aneurysm-in-apolipoprotein-e-deficient-mice
#20
Le Yang, Lin Shen, Gang Li, Hai Yuan, Xing Jin, Xuejun Wu
BACKGROUND AND AIMS: We aimed to determine the effect of HIF-1α, the main regulatory subunit of the hypoxia inducible factor 1 (HIF-1), on the development of the abdominal aortic aneurysm (AAA). METHODS: AAA was induced in ApoE(-/-) mice by angiotensinⅡ (AngⅡ) infusion. In vivo silencing of HIF-1α was achieved by transfection of lentivirus expressing HIF-1α shRNA. RESULTS: Time course analysis of the AngⅡ infusion model revealed that HIF-1α was persistently upregulated during a 28-day period of AAA development...
September 2016: Atherosclerosis
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