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Mmp aneurysm

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.)
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
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
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
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
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
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
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
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
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
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
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
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
Tomonaga Ameku, Daisuke Taura, Masakatsu Sone, Tomohiro Numata, Masahiro Nakamura, Fumihiko Shiota, Taro Toyoda, Satoshi Matsui, Toshikazu Araoka, Tetsuhiko Yasuno, Shin-Ichi Mae, Hatasu Kobayashi, Naoya Kondo, Fumiyo Kitaoka, Naoki Amano, Sayaka Arai, Tomoko Ichisaka, Norio Matsuura, Sumiko Inoue, Takuya Yamamoto, Kazutoshi Takahashi, Isao Asaka, Yasuhiro Yamada, Yoshifumi Ubara, Eri Muso, Atsushi Fukatsu, Akira Watanabe, Yasunori Sato, Tatsutoshi Nakahata, Yasuo Mori, Akio Koizumi, Kazuwa Nakao, Shinya Yamanaka, Kenji Osafune
Cardiovascular complications are the leading cause of death in autosomal dominant polycystic kidney disease (ADPKD), and intracranial aneurysm (ICA) causing subarachnoid hemorrhage is among the most serious complications. The diagnostic and therapeutic strategies for ICAs in ADPKD have not been fully established. We here generated induced pluripotent stem cells (iPSCs) from seven ADPKD patients, including four with ICAs. The vascular cells differentiated from ADPKD-iPSCs showed altered Ca(2+) entry and gene expression profiles compared with those of iPSCs from non-ADPKD subjects...
2016: Scientific Reports
Simon W Rabkin
BACKGROUND: Aortic aneurysms (AAs) are without effective pharmacologic therapy, in clinical usage, in part because of the limited understanding of factors leading to AA development. OBJECTIVE: The objectives of this study were to examine the evidence that cigarette smoking induces AAs through altering matrix metalloproteinases (MMP) and the molecular biology/pharmacology that maybe involved in this effect. METHODS: A systematic search was conducted to identify studies that examined the links between cigarette smoke, MMP and AAs...
June 24, 2016: Current Vascular Pharmacology
Shih-Hung Tsai, Po-Hsun Huang, Yu-Juei Hsu, Yi-Jen Peng, Chien-Hsing Lee, Jen-Chun Wang, Jaw-Wen Chen, Shing-Jong Lin
Hypoxia inducible factor-1α (HIF-1α) pathway is associated with many vascular diseases, including atherosclerosis, arterial aneurysms, pulmonary hypertension and chronic venous diseases. Significant HIF-1α expression could be found at the rupture edge at human abdominal aortic aneurysm (AAA) tissues. While our initial in vitro experiments had shown that deferoxamine (DFO) could attenuate angiotensin II (AngII) induced endothelial activations; we unexpectedly found that DFO augmented the severity of AngII-induced AAA, at least partly through increased accumulation of HIF-1α...
2016: Scientific Reports
Ingrid Gomez, Gulsev Ozen, Catherine Deschildre, Yasmine Amgoud, Lilia Boubaya, Isabelle Gorenne, Chabha Benyahia, Thomas Roger, Guy Lesèche, Erwan Galardon, Gokce Topal, Marie-Paule Jacob, Dan Longrois, Xavier Norel
Hydrogen sulfide (H2S) is a mediator with demonstrated protective effects for the cardiovascular system. On the other hand, prostaglandin (PG)E2 is involved in vascular wall remodeling by regulating matrix metalloproteinase (MMP) activities. We tested the hypothesis that endogenous H2S may modulate PGE2, MMP-1 activity and endogenous tissue inhibitors of MMPs (TIMP-1/-2). This regulatory pathway could be involved in thinning of abdominal aortic aneurysm (AAA) and thickening of saphenous vein (SV) varicosities...
2016: PloS One
Thibaut Triglia, Anna Mezzapesa, Jean Charles Martin, Monique Verdier, David Lagier, Henry Dufour, Nicolas Bruder, Marie-Christine Alessi, Lionel J Velly
BACKGROUND: Delayed cerebral ischaemia from vasospasm is an important cause of complications and death after aneurysmal subarachnoid haemorrhage. There is currently no established biomarker for identifying patients at high risk of delayed cerebral ischaemia. OBJECTIVE: Considering the important role of inflammation in the pathogenesis of delayed cerebral ischaemia, we investigated whether matrix metalloproteinase-9 (MMP-9) may be an efficient biomarker for predicting elayed cerebral ischaemia after subarachnoid haemorrhage...
September 2016: European Journal of Anaesthesiology
Masaaki Korai, Keiko T Kitazato, Yoshiteru Tada, Takeshi Miyamoto, Kenji Shimada, Nobuhisa Matsushita, Yasuhisa Kanematsu, Junichiro Satomi, Tomoki Hashimoto, Shinji Nagahiro
BACKGROUND: Hyperhomocysteinemia (HHcy) is associated with inflammation and a rise in the expression of matrix metalloproteinase-9 (MMP-9) in the vascular wall. However, the role of HHcy in the growth and rupture of cerebral aneurysms remains unclear. METHODS: Thirteen-week-old female Sprague-Dawley rats were subject to bilateral ovariectomy and ligation of the right common carotid artery and fed an 8 % high-salt diet to induce cerebral aneurysms. Two weeks later, they underwent ligation of the bilateral posterior renal arteries...
2016: Journal of Neuroinflammation
Fang Wang, Houzao Chen, Yunfei Yan, Yue Liu, Shuyang Zhang, Depei Liu
An abdominal aortic aneurysm (AAA) is a permanent, localized dilatation of the abdominal aorta. In western countries, the morbidity of AAA is approximately 8%. Currently, pharmacotherapies for AAA are limited. Here, we demonstrate that baicalein (BAI), the main component of the Chinese traditional drug "Huang Qin", attenuates the incidence and severity of AAA in Apoe (-/-) mice infused with angiotensin II (AngII). Mechanically, BAI treatment decreases AngII-induced reactive oxygen species (ROS) production in the aortic wall...
September 2016: Science China. Life Sciences
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