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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
Hidemi Takeuchi, Michihiro Okuyama, Haruhito A Uchida, Yuki Kakio, Ryoko Umebayashi, Yuka Okuyama, Yasuhiro Fujii, Susumu Ozawa, Masashi Yoshida, Yu Oshima, Shunji Sano, Jun Wada
BACKGROUND AND AIMS: Chronic kidney disease (CKD) and diabetes mellitus (DM) are considered as risk factors for cardiovascular diseases. The purpose of this study was to clarify the relationship of CKD and DM with the presence of abdominal aortic aneurysm (AAA). METHODS: We enrolled 261 patients with AAA (AAA+) and age-and-sex matched 261 patients without AAA (AAA-) at two hospitals between 2008 and 2014, and examined the association between the risk factors and the presence of AAA...
2016: PloS One
Anup Arumughan, Yvette Roske, Carolin Barth, Laura Lleras Forero, Kenny Bravo-Rodriguez, Alexandra Redel, Simona Kostova, Erik McShane, Robert Opitz, Katja Faelber, Kirstin Rau, Thorsten Mielke, Oliver Daumke, Matthias Selbach, Elsa Sanchez-Garcia, Oliver Rocks, Daniela Panáková, Udo Heinemann, Erich E Wanker
Interaction mapping is a powerful strategy to elucidate the biological function of protein assemblies and their regulators. Here, we report the generation of a quantitative interaction network, directly linking 14 human proteins to the AAA+ ATPase p97, an essential hexameric protein with multiple cellular functions. We show that the high-affinity interacting protein ASPL efficiently promotes p97 hexamer disassembly, resulting in the formation of stable p97:ASPL heterotetramers. High-resolution structural and biochemical studies indicate that an extended UBX domain (eUBX) in ASPL is critical for p97 hexamer disassembly and facilitates the assembly of p97:ASPL heterotetramers...
October 20, 2016: Nature Communications
Priyanka Dutta, Ahnaf Siddiqui, Mohsen Botlani, Sameer Varma
Nipah is an emerging paramyxovirus that is of serious concern to human health. It invades host cells using two of its membrane proteins-G and F. G binds to host ephrins and this stimulates G to activate F. Upon activation, F mediates virus-host membrane fusion. Here we focus on mechanisms that underlie the stimulation of G by ephrins. Experiments show that G interacts with ephrin and F through separate sites located on two different domains, the receptor binding domain (RBD) and the F activation domain (FAD)...
October 18, 2016: Biophysical Journal
T Christian Gasser
Abdominal aortic aneurysm (AAA) rupture is a local event in the aneurysm wall that naturally demands tools to assess the risk for local wall rupture. Consequently, global parameters like the maximum diameter and its expansion over time can only give very rough risk indications; therefore, they frequently fail to predict individual risk for AAA rupture. In contrast, the Biomechanical Rupture Risk Assessment (BRRA) method investigates the wall's risk for local rupture by quantitatively integrating many known AAA rupture risk factors like female sex, large relative expansion, intraluminal thrombus-related wall weakening, and high blood pressure...
April 2016: Aorta (Stamford, Conn.)
Karina Di Gregoli, Nur Najmi Mohamad Anuar, Rosaria Bianco, Stephen J White, Andrew C Newby, Sarah J George, Jason L Johnson
RATIONALE: Atherosclerosis and aneurysms are leading causes of mortality worldwide. MicroRNAs (miRs) are key determinants of gene and protein expression, and atypical miR expression has been associated with a number of cardiovascular diseases; although their contributory role to atherosclerotic plaque and abdominal aortic aneurysm (AAA) stability are poorly understood. OBJECTIVE: To investigate whether miR-181b regulates TIMP-3 expression and affects atherosclerosis and aneurysms Methods and Results: Here, we demonstrate that miR-181b was over-expressed in symptomatic human atherosclerotic plaques and abdominal aortic aneurysms, and correlated with decreased expression of predicted miR-181b targets, TIMP-3 and elastin...
October 18, 2016: Circulation Research
J R Boyle
No abstract text is available yet for this article.
October 15, 2016: European Journal of Vascular and Endovascular Surgery
Nickias Kienle, Tobias H Kloepper, Dirk Fasshauer
BACKGROUND: A defining feature of eukaryotic cells is the presence of various distinct membrane-bound compartments with different metabolic roles. Material exchange between most compartments occurs via a sophisticated vesicle trafficking system. This intricate cellular architecture of eukaryotes appears to have emerged suddenly, about 2 billion years ago, from much less complex ancestors. How the eukaryotic cell acquired its internal complexity is poorly understood, partly because no prokaryotic precursors have been found for many key factors involved in compartmentalization...
October 18, 2016: BMC Evolutionary Biology
Ramona Jühlen, Dana Landgraf, Angela Huebner, Katrin Koehler
It has been shown that the nucleoporin ALADIN plays a significant role in the redox homeostasis of the cell but its function in steroidogenesis contributing to adrenal atrophy in triple A syndrome remains largely unknown. In an attempt to identify new interaction partners of ALADIN, co-immunoprecipitation followed by proteome analysis was conducted in different expression models using the human adrenocortical tumour cell line NCI-H295R. Our results suggest an interaction of ALADIN with the microsomal protein PGRMC2...
October 17, 2016: Biology Open
Xiongjing Jiang
Abdominal aortic aneurysm (AAA) is an important cause of mortality in older adults. Most AAAs are asymptomatic and screening programs have been introduced to identify AAAs. There is currently some recommendations for medical optimisation of patients with AAA, such as anti-hypertension, statin, Anti-platelet therapy, B-blockade, et al. Some medical treatments to limit progression of small AAAs, which have examined the potential of targeting inflammation, proteolysis, the renin-angiotensin system, the coagulation system and sex hormones as approaches to limiting AAA pathogenesis are investigated as well as...
September 2016: Journal of Hypertension
Chrisovalantis Papadopoulos, Philipp Kirchner, Monika Bug, Daniel Grum, Lisa Koerver, Nina Schulze, Robert Poehler, Alina Dressler, Sven Fengler, Khalid Arhzaouy, Vanda Lux, Michael Ehrmann, Conrad C Weihl, Hemmo Meyer
Rupture of endosomes and lysosomes is a major cellular stress condition leading to cell death and degeneration. Here, we identified an essential role for the ubiquitin-directed AAA-ATPase, p97, in the clearance of damaged lysosomes by autophagy. Upon damage, p97 translocates to lysosomes and there cooperates with a distinct set of cofactors including UBXD1, PLAA, and the deubiquitinating enzyme YOD1, which we term ELDR components for Endo-Lysosomal Damage Response. Together, they act downstream of K63-linked ubiquitination and p62 recruitment, and selectively remove K48-linked ubiquitin conjugates from a subpopulation of damaged lysosomes to promote autophagosome formation...
October 17, 2016: EMBO Journal
Yuandong Li, Woo June Choi, Wan Qin, Utku Baran, Lauren M Habenicht, Ruikang K Wang
BACKGROUND: Arteriogenesis describes the active growth of the pre-existing collateral arterioles, which is a crucial tissue-saving process in occlusive vascular diseases. NEW METHOD: We propose to use optical coherence tomography (OCT)-based microangiography (OMAG) to monitor arteriogenesis following artery transection in mouse ear and focal stroke in mouse brain. RESULTS: Our longitudinal mouse ear study shows that the growth phase of arteriogenesis, indicated by changes in collateral vessel diameter and velocity, occurs between 12-24hours after vessel occlusion...
October 14, 2016: Journal of Neuroscience Methods
Sergio Ruiz de Galarreta, Raúl Antón, Aitor Cazon, Gorka S Larraona, Ender A Finol
An Abdominal Aortic Aneurysm (AAA) is a permanent focal dilatation of the abdominal aorta at least 1.5 times its normal diameter. The criterion of maximum diameter is still used in clinical practice, although numerical studies have demonstrated the importance of other biomechanical factors. Numerical studies, however, must be validated experimentally before they can be clinically implemented. We have developed a methodology for manufacturing anisotropic AAA replicas with non-uniform wall thickness. Different composites were fabricated and tested, and one was selected in order to manufacture a phantom with the same properties...
October 10, 2016: Medical Engineering & Physics
Sirui Zhou, Amirthagowri Ambalavanan, Daniel Rochefort, Pingxing Xie, Cynthia V Bourassa, Pascale Hince, Alexandre Dionne-Laporte, Dan Spiegelman, Ziv Gan-Or, Cathy Mirarchi, Vessela Zaharieva, Nicolas Dupré, Hatasu Kobayashi, Toshiaki Hitomi, Kouji Harada, Akio Koizumi, Lan Xiong, Patrick A Dion, Guy A Rouleau
Intracranial aneurysms (IAs) are the result of focal weakness in the artery wall and have a complex genetic makeup. To date, genome-wide association and sequencing studies have had limited success in identifying IA risk factors. Distinct populations, such as the French-Canadian (FC) population, have increased IA prevalence. In our study, we used exome sequencing to prioritize risk variants in a discovery cohort of six FC families affected by IA, and the analysis revealed an increased variation burden for ring finger protein 213 (RNF213)...
September 30, 2016: American Journal of Human Genetics
Anahita Dua, Steven Koprowski, Gilbert Upchurch, Cheong J Lee, Sapan S Desai
BACKGROUND: In 2014, we published a series of articles in the Journal of Vascular Surgery that detailed the decrease in volume of open aneurysm repair (OAR) completed for abdominal aortic aneurysm (AAA) by vascular surgery trainees. At that time, only data points from 2000 through 2011 were available, and reliable predictions could only be made through 2015. Lack of data on endovascular aneurysm repair (EVAR) using fenestrated (FEVAR) and branched (BrEVAR) endografts also affected our findings...
October 12, 2016: Journal of Vascular Surgery
Gergely N Nagy, Reynier Suardiaz, Anna Lopata, Olivér Ozohanics, Károly Vékey, Bernard R Brooks, Ibolya Leveles, Judit Toth, Beata G Vertessy, Edina Rosta
Arginine finger is a highly conserved and essential residue in many GTPase and AAA+ ATPase enzymes that completes the active site from a distinct protomer, forming contacts with the γ-phosphate of the nucleotide. To date, no pyrophosphatase has been identified that employs an arginine finger fulfilling all the above properties, all essential arginine fingers are used to catalyze the cleavage of the γ-phosphate. Here, we identify and unveil the role of a conserved arginine residue in trimeric dUTPases that meets all the criteria established for arginine fingers...
October 14, 2016: Journal of the American Chemical Society
Tomomi Nakajima, Masataka Sato, Akito Imai, Yasunori Watanabe
A 79-year-old man underwent endovascular repair for abdominal aortic aneurysm (AAA), and both internal iliac arteries (IIAs) were preserved. Postoperatively, loss of appetite developed. On the fifth day, computerized tomography (CT) showed inferior mesenteric artery thrombus formation, necrosis of the descending colon and rectum, and generalized peritonitis. The endovascular devices had not migrated. A colonic resection was performed. Histological analysis confirmed intestinal necrosis associated with mesenteric thrombus...
2016: Annals of Vascular Diseases
Timothy Wai, Shotaro Saita, Hendrik Nolte, Sebastian Müller, Tim König, Ricarda Richter-Dennerlein, Hans-Georg Sprenger, Joaquin Madrenas, Mareike Mühlmeister, Ulrich Brandt, Marcus Krüger, Thomas Langer
The SPFH (stomatin, prohibitin, flotillin, HflC/K) superfamily is composed of scaffold proteins that form ring-like structures and locally specify the protein-lipid composition in a variety of cellular membranes. Stomatin-like protein 2 (SLP2) is a member of this superfamily that localizes to the mitochondrial inner membrane (IM) where it acts as a membrane organizer. Here, we report that SLP2 anchors a large protease complex composed of the rhomboid protease PARL and the i-AAA protease YME1L, which we term the SPY complex (for SLP2-PARL-YME1L)...
October 13, 2016: EMBO Reports
Sam Taylor, Ian Thomson, Jo Krysa
AIM: A ruptured abdominal aortic aneurysm (rAAA) remains a significant threat to life, with a 30-50% in-hospital mortality rate. The recent introduction of emergency endovascular aneurysm repair (rEVAR) in New Zealand presents an alternative to open repair for rAAAs. The aim of this paper is to review the current experience in New Zealand in the repair of rAAAs. METHODS: Data from the Australasian Vascular Audit (AVA) was reviewed, with data pertaining to rAAAs collected for the five-year period from January 2010 to December 2014...
October 14, 2016: New Zealand Medical Journal
Prasad Kottayil Padmanabhan, Ouafa Zghidi-Abouzid, Mukesh Samant, Carole Dumas, Bruno Guedes Aguiar, Jerome Estaquier, Barbara Papadopoulou
DDX3 is a highly conserved member of ATP-dependent DEAD-box RNA helicases with multiple functions in RNA metabolism and cellular signaling. Here, we describe a novel function for DDX3 in regulating the mitochondrial stress response in the parasitic protozoan Leishmania. We show that genetic inactivation of DDX3 leads to the accumulation of mitochondrial reactive oxygen species (ROS) associated with a defect in hydrogen peroxide detoxification. Upon stress, ROS production is greatly enhanced, causing mitochondrial membrane potential loss, mitochondrial fragmentation, and cell death...
October 13, 2016: Cell Death & Disease
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