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"coagulation" and"endothelial cell"

Risa Inagawa, Hideshi Okada, Genzou Takemura, Kodai Suzuki, Chihiro Takada, Hirohisa Yano, Yoshiaki Ando, Takahiro Usui, Yasuaki Hotta, Nagisa Miyazaki, Akiko Tsujimoto, Ryogen Zaikokuji, Atsumu Matsumoto, Tomonori Kawaguchi, Tomoaki Doi, Takahiro Yoshida, Shozo Yoshida, Keisuke Kumada, Hiroaki Ushikoshi, Izumi Toyoda, Shinji Ogura
BACKGROUND: The most recent diagnostic criteria for sepsis includes organ failure. Microvascular endothelial injury is thought to lead to the multiple organ failure seen in sepsis, although the precise mechanism is still controversial. Acute respiratory distress syndrome (ARDS) is the primary complication during the sequential development of multiple organ dysfunction in sepsis, and endothelial injury is deeply involved. Sugar-protein glycocalyx coats all healthy vascular endothelium, and its disruption is one factor thought to contribute to microvascular endothelial dysfunction during sepsis...
March 16, 2018: Chest
Ying Su, Jingli Chen, Zengxiang Dong, Yan Zhang, Ruishuang Ma, Junjie Kou, Feng Wang, Jialan Shi
BACKGROUND/AIMS: The mechanisms for thrombosis in diabetic retinopathy (DR) are complex and need to be further elucidated. The purpose of this study was to test phosphatidylserine (PS) exposure on microparticles (MPs) and MP-origin cells from the circulation and to analyze cell-/MP-associated procoagulant activity (PCA) in DR patients. METHODS: PS-positive MPs and cells from healthy controls (n = 20) and diabetic patients (n = 60) were analyzed by flow cytometry and confocal microscopy...
March 15, 2018: Cellular Physiology and Biochemistry
Kondababu Kurakula, Duco S Koenis, Mark A Herzik, Yanyun Liu, John W Craft, Pieter B van Loenen, Mariska Vos, M Khang Tran, Henri H Versteeg, Marie-José T H Goumans, Wolfram Ruf, Carlie J M de Vries, Mehmet Şen
Tissue Factor is a cell-surface glycoprotein expressed in various cells of the vasculature and is the principal regulator of the blood coagulation cascade and hemostasis. Notably, aberrant expression of Tissue Factor is associated with cardiovascular pathologies such as atherosclerosis and thrombosis. Here, we sought to identify factors that regulate Tissue Factor gene expression and activity. Tissue Factor gene expression is regulated by various transcription factors, including activating protein-1 and nuclear factor-kappa B...
March 15, 2018: Haematologica
Lixiu Wang, Yayan Bi, Muxin Yu, Tao Li, Dongxia Tong, Xiaoyan Yang, Cong Zhang, Li Guo, Chunxu Wang, Yan Kou, Zengxiang Dong, Valerie A Novakovic, Ye Tian, Junjie Kou, Masood A Shammas, Jialan Shi
BACKGROUND: The definitive role of phosphatidylserine (PS) in the prothrombotic state of non-valvular atrial fibrillation (NVAF) remains unclear. Our objectives were to study the PS exposure on blood cells and microparticles (MPs) in NVAF, and evaluate their procoagulant activity (PCA). METHODS: NVAF patients without (n = 60) and with left atrial thrombi (n = 18) and controls (n = 36) were included in our study. Exposed PS was analyzed with flow cytometry and confocal microscopy...
May 1, 2018: International Journal of Cardiology
Hui Zhong, Hidenori Wake, Keyue Liu, Yuan Gao, Kiyoshi Teshigawara, Masakiyo Sakaguchi, Shuji Mori, Masahiro Nishibori
The apoptotic process of erythrocytes is known as eryptosis, and is characterized by phosphatidylserine (PS) expression on the outer membrane. PS-positive erythrocytes are increased in sepsis, and PS is believed to facilitate coagulation of erythrocytes and activate macrophages. However, the relationship between eryptosis and abnormal coagulation in sepsis is still not fully understood. Histidine-rich glycoprotein (HRG) inhibits immunothrombus formation by regulating neutrophils and vascular endothelial cells...
November 24, 2017: Journal of Pharmacological Sciences
Liaoran Wang, David K C Cooper, Lars Burdorf, Yi Wang, Hayato Iwase
There has recently been considerable progress in the results of pig organ transplantation in nonhuman primates (NHPs), largely associated with the availability of (i) pigs genetically-engineered to overcome coagulation dysregulation, and (ii) novel immunosuppressive agents. The barriers of thrombotic microangiopathy and/or consumptive coagulation were believed to be associated with (i) activation of the graft vascular endothelial cells (VECs) by a low level of anti-pig antibody binding and/or complement deposition and/or innate immune cell activity, and (ii) molecular incompatibilities between the NHP and pig coagulation-anticoagulation systems...
March 10, 2018: Transplantation
Vivek Krishna Pulakazhi Venu, Mahmoud Saifeddine, Koichiro Mihara, Mahmoud El-Daly, Darrell Belke, Jonathan L E Dean, Edward R O'Brien, Simon A Hirota, Morley D Hollenberg
BACKGROUND AND PURPOSE: Previously, we demonstrated that exogenous Heat Shock Protein 27 (HSP27/gene, HSPB1) treatment of human endothelial progenitor cells (EPCs) increases the synthesis and secretion of VEGF, improves EPC-migration/re-endothelialization and decreases neo-intima formation, suggesting a role for HSPB1 in regulating EPC function. We hypothesized that HSPB1 could also affect mature endothelial cells (ECs) to alter EC-mediated vasoreactivity in vivo. Our work focused on eNOS/NO-dependent relaxation caused by acetylcholine and the coagulation pathway-activated receptor, proteinase-activated receptor-2 (PAR2)...
March 12, 2018: British Journal of Pharmacology
Muxin Yu, Rujuan Xie, Yan Zhang, Hui Liang, Li Hou, Chengyuan Yu, Jinming Zhang, Zengxiang Dong, Ye Tian, Yayan Bi, Junjie Kou, Valerie A Novakovic, Jialan Shi
Background: Relatively little is known about the role of phosphatidylserine (PS) in procoagulant activity (PCA) in patients with diabetic kidney disease (DKD). This study was designed to evaluate whether exposed PS on microparticles (MPs) and MP-origin cells were involved in the hypercoagulability in DKD patients. Methods: DKD patients (n = 90) were divided into three groups based on urinary albumin excretion rate, defined as normoalbuminuria (No-A) (<30 mg/24 h), microalbuminuria (Mi-A) (30-299 mg/24 h) or macroalbuminuria (Ma-A) (>300 mg/24 h), and compared with healthy controls (n = 30)...
February 26, 2018: Nephrology, Dialysis, Transplantation
Mahmoud Abd-Elkareem, Nasser S Abou Khalil, Alaa H Sayed
4-Nonylphenol (NP) toxicity in fish attracts much attention due to its ability in targeting several organs; however, the researches regarding its potential hepatotoxicity are conflicting and still require further investigation. Therefore, the objective of this study is to focus on this issue from the histophysiological point of view using NP intoxicated African catfish (Clarias gariepinus) as a model of hepatotoxicity. Twelve adult fish (6 per group) were divided into two groups; the first was considered as a control and the second was exposed to NP dissolved in water at a dose of 0...
March 7, 2018: Fish Physiology and Biochemistry
Fumihiro Sanada, Yoshiaki Taniyama, Jun Muratsu, Rei Otsu, Hideo Shimizu, Hiromi Rakugi, Ryuichi Morishita
Cellular senescence is the complex process of deterioration that drives the aging of an organism, resulting in the progressive loss of organ function and eventually phenotypic aging. Senescent cells undergo irreversible growth arrest, usually by inducing telomere shortening. Alternatively, senescence may also occur prematurely in response to various stress stimuli, such as oxidative stress, DNA damage, or activated oncogenes. Recently, it has been shown that IGF binding protein-5 (IGFBP-5) with the induction of the tumor suppressor p53 is upregulated during cellular senescence...
2018: Frontiers in Endocrinology
Bridget Shafit-Zagardo, Ross C Gruber, Juwen C DuBois
Tyro3, Axl, and Mertk, referred to as the TAM family of receptor tyrosine kinases, are instrumental in maintaining cell survival and homeostasis in mammals. TAM receptors interact with multiple signaling molecules to regulate cell migration, survival, phagocytosis and clearance of metabolic products and cell debris called efferocytosis. The TAMs also function as rheostats to reduce the expression of proinflammatory molecules and prevent autoimmunity. All three TAM receptors are activated in a concentration-dependent manner by the vitamin K-dependent growth arrest-specific protein 6 (Gas6)...
March 4, 2018: Pharmacology & Therapeutics
Fumihiko Nagano, Tomohiro Mizuno, Shuji Mizumoto, Kengo Yoshioka, Kazuo Takahashi, Naotake Tsuboi, Shoichi Maruyama, Shuhei Yamada, Tadashi Nagamatsu
Extracellular histones induce lethal thrombosis by promoting platelet aggregation, neutrophil migration, and cell injuries. Heparin, which has negative charges, can bind to extracellular histones; however, heparin strongly inhibits the activation of coagulation. Since chondroitin sulfate (CS) shows less effect on the coagulation system than heparin does, CS has the potential to become an effective drug for lethal thrombosis with high risk of bleeding. To elucidate the therapeutic mechanisms of CS in lethal thrombosis, we investigated the interaction between CS and extracellular histones...
February 28, 2018: European Journal of Pharmacology
Bryan F Burkey, Niel C Hoglen, Philip Inskeep, Margaret Wyman, Thomas E Hughes, James E Vath
Methionine aminopeptidase 2 (MetAP2) inhibition is a promising approach to treating diabetes, obesity, and associated metabolic disorders. Beloranib, a MetAP2 inhibitor previously investigated for treatment of Prader-Willi syndrome, was associated with venous thrombotic adverse events likely resulting from drug effects on vascular endothelial cells (ECs). Here, we report the pharmacological characterization of ZGN-1061, a novel MetAP2 inhibitor being investigated for treatment of diabetes and obesity. Four weeks of subcutaneous administration of ZGN-1061 to diet-induced obese (DIO) insulin-resistant mice produced a 25% reduction in body weight, primarily due to reduced fat mass, that was comparable to beloranib...
February 28, 2018: Journal of Pharmacology and Experimental Therapeutics
Bao Q Wang, Meng Shi, Jian P Zhang, Xie Wu, Mei J Chang, Zhi H Chen, Hua H Shen, Yuan L Song, Jian Zhou, Chun X Bai
BACKGROUND: As activation of the coagulation system is both a consequence and contributor to acute lung injury (ALI), pulmonary coagulopathy has become a potential target for therapeutic intervention in ALI patients. We investigated the effects and possible mechanisms of endothelial cell (EC)-anchored tissue factor pathway inhibitor (TFPI) on lipopolysaccharide (LPS)-induced ALI in mice. METHODS: To assess the effect of endothelial cell-anchored TFPI deletion on ALI indices, TFPI knockout (cKO) mice were generated...
February 12, 2018: Shock
Suping Li, Qiao Jiang, Shaoli Liu, Yinlong Zhang, Yanhua Tian, Chen Song, Jing Wang, Yiguo Zou, Gregory J Anderson, Jing-Yan Han, Yung Chang, Yan Liu, Chen Zhang, Liang Chen, Guangbiao Zhou, Guangjun Nie, Hao Yan, Baoquan Ding, Yuliang Zhao
Nanoscale robots have potential as intelligent drug delivery systems that respond to molecular triggers. Using DNA origami we constructed an autonomous DNA robot programmed to transport payloads and present them specifically in tumors. Our nanorobot is functionalized on the outside with a DNA aptamer that binds nucleolin, a protein specifically expressed on tumor-associated endothelial cells, and the blood coagulation protease thrombin within its inner cavity. The nucleolin-targeting aptamer serves both as a targeting domain and as a molecular trigger for the mechanical opening of the DNA nanorobot...
March 2018: Nature Biotechnology
Beth M French, Selin Sendil, Krishna Mohan Sepuru, Jolene Ranek, Lars Burdorf, Donald Harris, Emily Redding, Xiangfei Cheng, Christopher T Laird, Yuming Zhao, Benjamin Cerel, Krishna Rajarathnam, Richard N Pierson, Agnes M Azimzadeh
BACKGROUND: Human neutrophils are sequestered by pig lung xenografts within minutes during ex vivo perfusion. This phenomenon is not prevented by pig genetic modifications that remove xeno-antigens or added human regulatory molecules intended to down-regulate activation of complement and coagulation pathways. This study investigated whether recipient and donor interleukin-8 (IL-8), a chemokine known to attract and activate neutrophils during inflammation, is elaborated in the context of xenogeneic injury, and whether human or pig IL-8 promote the adhesion of human neutrophils in in vitro xenograft models...
February 9, 2018: Xenotransplantation
T O'Herron, J Lafferty
Radiation therapy is one of the primary treatments in fighting breast cancer, one of the most common cancers in the US. One of the dose limiting factors of this therapy is radiation induced heart damage that results from mediastinal radiation. Recently statins, a medication typically used to lower cholesterol levels, have been suggested as a prophylactic treatment to potentially mitigate this process. Similarly, we hypothesized whether colchicine, an anti-inflammatory medication that is presently used in the treatment of gout and pericarditis, might be used to prevent coronary artery disease induced by radiation therapy...
February 2018: Medical Hypotheses
Naomi Sanda, Nobuaki Suzuki, Atsuo Suzuki, Takeshi Kanematsu, Mayuko Kishimoto, Hidetoshi Hasuwa, Akira Takagi, Tetsuhito Kojima, Tadashi Matsushita, Shigeo Nakamura
Von Willebrand factor (VWF) is synthesized in megakaryocytes and endothelial cells (ECs) and has two main roles: to carry and protect coagulation factor VIII (FVIII) from degradation by forming VWF-FVIII complex; and to mediate platelet adhesion and aggregation at sites of vascular injury. Previous research using the HEK293 cell line revealed that the VWF K1362 mutation interacted directly with platelet glycoprotein Ib (GPIb). Vwf K1362A knock-in (KI) mice were therefore generated to verify the in vivo function of residue 1362 in binding to platelet GPIb...
February 1, 2018: International Journal of Hematology
Tugba Ugurlu, Candan Ozogul, Gulistan Sanem Saribas, Seren Gulsen Gurgen, Seda Nur Akyol, Bahar Kartal
The aim of this study was to investigate the effect of antioxidants on angiogenesis in uterine transplantation. We used 24 female rats equally divided into four groups: Group 1 had the uterus stored in HTK (Histidine-Tryptophan-Ketoglutarate) solution at 4 °C cold storage for 4 h. Group 2 had the uterine tissue stored in HTK solution combined with acetyl L-carnitine (10-8  M) for 4 h at +4 °C. The same procedures with Group 1 and 2 were repeated for 24 h for Groups 3 and 4, respectively. Histological investigation and immunohistochemical analysis were performed...
January 31, 2018: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
S B Cho, J Na, Z Zheng, J M Lim, J-S Kang, J H Lee, S E Lee
BACKGROUND: Bipolar, alternating current radiofrequency (RF) conduction using invasive noninsulated electrodes consecutively generates independent tissue coagulation around each electrode and then, the converged coagulation columns. METHODS: Two pulsed-type RF models at the on-time pulse width/pulse pack of 30 and 40 milliseconds were designed to amplify the early stage of RF-induced tissue reaction using hairless mouse skin in vivo. Then, structural and ultrastructural changes were evaluated in hairless mouse skin samples at baseline and immediately 1 day, 3 days, 7 days, and 14 days after treatment...
January 25, 2018: Skin Research and Technology
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