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WT-1 vascular

Hayato Ogawa, Koji Ohashi, Masanori Ito, Rei Shibata, Noriyoshi Kanemura, Daisuke Yuasa, Takahiro Kambara, Kazuhiro Matsuo, Satoko Hayakawa, Mizuho Hiramatsu-Ito, Naoya Otaka, Hiroshi Kawanishi, Shukuro Yamaguchi, Takashi Enomoto, Takaya Abe, Mari Kaneko, Mikito Takefuji, Toyoaki Murohara, Noriyuki Ouchi
AIMS: Secreted factors produced by adipose tissue are involved in the pathogenesis of cardiovascular disease. We previously identified adipolin, also known as C1q/Tnf-related protein 12, as an insulin-sensitizing adipokine. However, the role of adipolin in vascular disease remains unknown. Here, we investigated whether adipolin modulates pathological vascular remodeling. METHODS AND RESULTS: Adipolin-knockout (APL-KO) and wild-type (WT) mice were subjected to wire-induced injury of the femoral artery...
March 15, 2019: Cardiovascular Research
Ping Li, Christine Schille, Ernst Schweizer, Evi Kimmerle-Müller, Frank Rupp, Alexander Heiss, Claudia Legner, Ulrich E Klotz, Jürgen Geis-Gerstorfer, Lutz Scheideler
Zinc (Zn) alloys have been considered as promising absorbable metals, mainly due to their moderate degradation rates ranging between magnesium alloys and iron alloys. The degradation behavior depends on the specific physiological environment. Released metallic ions and corrosion products directly influence biocompatibility. The initial contact of orthopedic implants or vascular stents after implantation will be with blood. In this study, fetal bovine serum (FBS) was used as a model system of blood components...
March 9, 2019: Acta Biomaterialia
Evren Caglayan, Manuela Trappiel, Arnica Behringer, Eva Maria Berghausen, Margarete Odenthal, Ernst Wellnhofer, Kai Kappert
BACKGROUND: Obesity is associated with cardiovascular complications, including pulmonary hypertension (PH). Reports suggest that peroxisome proliferator-activated receptor-γ (PPARγ) has direct action in preventing vascular remodelling in PH. Here we dissected the specific role of high-fat-diet (HFD)-induced obesity and vascular smooth muscle cell (VSMC)-PPARγ for remodelling of small pulmonary arteries. METHODS: Wild-type (WT) and VSMC-specific PPARγ-knockout (SmPparγ-/- ) mice were fed a low-fat-diet (LFD, 10% kcal from fat) or HFD (60% kcal from fat) for 24 weeks...
February 27, 2019: Respiratory Research
Sathnur Pushpakumar, Sourav Kundu, Utpal Sen
The accumulation of homocysteine (Hcy) during chronic kidney failure (CKD) can exert toxic effects on the glomeruli and tubulo-interstitial region. Among the potential mechanisms, the formation of highly reactive metabolite, Hcy thiolactone, is known to modify proteins by N-homocysteinylation, leading to protein degradation, stress and impaired function. Previous studies documented impaired nitric oxide production and altered caveolin expression in hyperhomocysteinemia (HHcy), leading to endothelial dysfunction...
February 18, 2019: Scientific Reports
Qiang Gu, Jin-Chao Hou, Xiang-Ming Fang
Background/aim: Sphingosine 1-phosphate receptor 2 (S1PR2), a member of the seven-transmembrane receptor family, can be activated by its natural ligand sphingosine 1-phosphate (S1P) to initiate signal transduction and is involved in a wide range of biological effects such as immune cell migration and vascular permeability. Its relationship with neuropathic pain (NP) has not been reported. In this study, the effects of S1PR2 on the development of NP were studied. Materials and methods: We generated a model of NP by partial sciatic nerve ligation (pSNL)...
February 11, 2019: Turkish Journal of Medical Sciences
Takahiro Ohkura, Teizo Yoshimura, Masayoshi Fujisawa, Toshiaki Ohara, Rie Marutani, Kaya Usami, Akihiro Matsukawa
Chronic low-grade inflammation in visceral adipose tissues triggers the development of obesity-related insulin resistance, leading to the metabolic syndrome, a serious health condition with higher risk of cardiovascular disease, diabetes, and stroke. In the present study, we investigated whether Sprouty-related EVH1-domain-containing protein 2 (Spred2), a negative regulator of the Ras/Raf/ERK/MAPK pathway, plays a role in the development of high fat diet (HFD)-induced obesity, adipose tissue inflammation, metabolic abnormalities, and insulin resistance...
2019: Frontiers in Immunology
Chen Liu, Renna Luo, Wei Wang, Zhangzhe Peng, Gail V W Johnson, Rodney E Kellems, Yang Xia
Background: Although numerous recent studies have shown a strong link between inflammation and hypertension, the underlying mechanisms by which inflammatory cytokines induce hypertension remain to be fully elucidated. Hypertensive disorders are also associated with elevated pressor sensitivity. Tissue transglutaminase (TG2), a potent crosslinking enzyme, is known to be transcriptionally activated by inflammatory cytokines and stabilize angiotensin II (Ang II) receptor AT1 (AT1R) via ubiquitination-preventing posttranslational modification...
February 2, 2019: American Journal of Hypertension
Francisco E Velázquez, Marina Anastasiou, Francisco J Carrillo-Salinas, Njabulo Ngwenyama, Ane M Salvador, Tania Nevers, Pilar Alcaide
T helper type 17 lymphocytes (Th17 cells) infiltrate the central nervous system (CNS), induce inflammation and demyelination and play a pivotal role in the pathogenesis of multiple sclerosis (MS). Sialomucin CD43 is highly expressed in Th17 cells and mediates adhesion to endothelial selectin (E-selectin), an initiating step in Th17 cell recruitment to sites of inflammation. CD43-/- mice have impaired Th17 cell recruitment to the CNS and are protected from Experimental Autoimmune Encephalomyelitis (EAE), the mouse model of multiple sclerosis...
January 28, 2019: Immunology
Sara R Turner, Mona Chappellaz, Brittany Popowich, Anne A Wooldridge, Timothy A J Haystead, William C Cole, Justin A MacDonald
The role of the smoothelin-like 1 (SMTNL1) protein in mediating vascular smooth muscle contractile responses to intraluminal pressure was examined in resistance vessels. Mesenteric arterioles from wild type (WT) and SMTNL1 global knock-out (KO) mice were examined with pressure myography. SMTNL1 deletion was associated with enhanced myogenic tone in vessels isolated from male, but not female, mice. Intraluminal pressures greater than 40 mmHg generated statistically significant differences in myogenic reactivity between WT and KO vessels...
January 24, 2019: Scientific Reports
Shimrit Avraham, Ben Korin, Sharon Aviram, Dvir Shechter, Yuval Shaked, Ami Aronheim
The activating transcription factor 3 (ATF3) and the c-Jun dimerization protein 2 (JDP2) are members of the basic leucine zipper (bZIP) family of transcription factors. These proteins share a high degree of homology and both can activate or repress transcription. Deficiency of either one of them in the non-cancer host cells was shown to reduce metastases. As ATF3 and JDP2 compensate each other's function, we studied the double deficiency of ATF3 and JDP2 in the stromal tumor microenvironment. Here, we show that mice with ATF3 and JDP2 double deficiency (designated thereafter dKO) developed larger tumors with high vascular perfusion and increased cell proliferation rate compared to wild type (WT) mice...
January 22, 2019: Oncogene
Luke S Dingwell, Eric A Shikatani, Rickvinder Besla, Andrew S Levy, Danny D Dinh, Abdul Momen, Hangjun Zhang, Talat Afroze, Michelle B Chen, Felix Chiu, Craig A Simmons, Filio Billia, Jennifer L Gommerman, Rohan John, Scott Heximer, James W Scholey, Steffen-Sebastian Bolz, Clinton S Robbins, Mansoor Husain
The proto-oncogene c-myb (and corresponding nuclear transcription factor, c-Myb) regulates the proliferation and differentiation of hematologic and vascular smooth muscle cells; however, the role of c-Myb in blood pressure regulation is unknown. Here, we show that mice homozygous for a hypomorphic c-myb allele ( c-myb h/h ) conferring reduced c-Myb activity manifest reduced peripheral blood and kidney B220+ B-cells and have decreased systolic (104±2 versus 120±1 mm Hg; P<0.0001) and diastolic blood pressure (71±2 versus 83±1 mm Hg; P<0...
January 14, 2019: Hypertension
Hendrik Bartolomaeus, András Balogh, Mina Yakoub, Susanne Homann, Lajos Markó, Sascha Höges, Dmitry Tsvetkov, Alexander Krannich, Sebastian Wundersitz, Ellen G Avery, Nadine Haase, Kristin Kräker, Lydia Hering, Martina Maase, Kristina Kusche-Vihrog, Maria Grandoch, Jens Fielitz, Stefan Kempa, Maik Gollasch, Zhaxybay Zhumadilov, Samat Kozhakhmetov, Almagul Kushugulova, Kai-Uwe Eckardt, Ralf Dechend, Lars Christian Rump, Sofia K Forslund, Dominik N Müller, Johannes Stegbauer, Nicola Wilck
BACKGROUND: Arterial hypertension and its organ sequelae show characteristics of T cell mediated inflammatory diseases. Experimental anti-inflammatory therapies have been shown to ameliorate hypertensive end-organ damage. Recently, the CANTOS study targeting interleukin-1β demonstrated that anti-inflammatory therapy reduces cardiovascular risk. The gut microbiome plays pivotal role in immune homeostasis and cardiovascular health. Short-chain fatty acids (SCFA) are produced from dietary fiber by gut bacteria and affect host immune homeostasis...
December 4, 2018: Circulation
Aurélie Hautefort, Pedro Mendes-Ferreira, Jessica Sabourin, Grégoire Manaud, Thomas Bertero, Catherine Rücker-Martin, Marianne Riou, Rui Adão, Boris Manoury, Mélanie Lambert, Angèle Boet, Florence Lecerf, Valérie Domergue, Carmen Brás-Silva, Ana Maria Gomez, David Montani, Barbara Girerd, Marc Humbert, Fabrice Antigny, Frédéric Perros
BACKGROUND: Monoallelic mutations in the gene encoding bone morphogenetic protein receptor 2 ( Bmpr2) is the main genetic risk factor for heritable pulmonary arterial hypertension (hPAH) with incomplete penetrance. Several Bmpr2 transgenic mice have been reported, but have not been shown to develop mild spontaneous PAH (SPH). In this study, we examined whether rats with the Bmpr2 mutation were more susceptible to develop PAH. METHODS: The zinc finger nuclease method was used to establish rat lines with mutations in the Bmpr2 gene...
October 4, 2018: Circulation
Tomohiro Betto, Hideki Amano, Yoshiya Ito, Koji Eshima, Tsutomu Yoshida, Yoshio Matsui, Sakiko Yamane, Tomoyoshi Inoue, Fumisato Otaka, Kiyonori Kobayashi, Wasaburo Koizumi, Masabumi Shibuya, Masataka Majima
BACKGROUND: Ulcerative Colitis (UC) is an inflammatory bowel disease that affects the colon. The development of UC is regulated by immune cells. Previously, we showed that vascular endothelial growth factor receptor 1 (VEGFR1) tyrosine kinase (TK) signaling induces healing of mucosal damage by recruiting VEGFR1+ cells appear to be lineage monocyte cells. Recent studies show that development of UC correlates with the number of regulatory T cells (Tregs). Here, we investigated whether VEGFR1-TK signaling induces healing of UC via accumulation of Tregs or not...
December 19, 2018: Biomedicine & Pharmacotherapy
Genhong Yao, Jingjing Qi, Zhuoya Zhang, Saisai Huang, Linyu Geng, Wenchao Li, Weiwei Chen, Xiaojun Tang, Shiying Wang, Lingyun Sun
AIM: Cardiovascular complications related to atherosclerosis are major causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). However, the underlying mechanisms are not fully understood. Endothelial dysfunction has been identified as having involvement in pathogenesis of cardiovascular diseases and SLE. This study aims to evaluate endothelial cell injury in mice with the combination of lupus and atherosclerosis. METHODS: The mouse model of accelerated atherosclerosis in lupus (gld...
December 21, 2018: International Journal of Rheumatic Diseases
Raelene J Pickering, Christos Tikellis, Carlos J Rosado, Despina Tsorotes, Alexandra Dimitropoulos, Monique Smith, Olivier Huet, Ruth M Seeber, Rekhati Abhayawardana, Elizabeth Km Johnstone, Jonathan Golledge, Yutang Wang, Karin A Jandeleit-Dahm, Mark E Cooper, Kevin Dg Pfleger, Merlin C Thomas
Activation of the type 1 angiotensin II receptor (AT1) triggers proinflammatory signaling through pathways independent of classical Gq signaling that regulate vascular homeostasis. Here, we report that the AT1 receptor preformed a heteromeric complex with the receptor for advanced glycation endproducts (RAGE). Activation of the AT1 receptor by angiotensin II (Ang II) triggered transactivation of the cytosolic tail of RAGE and NF-κB-driven proinflammatory gene expression independently of the liberation of RAGE ligands or the ligand-binding ectodomain of RAGE...
December 10, 2018: Journal of Clinical Investigation
Monica Longo, Mesk Alrais, Esther H Tamayo, Francesca Ferrari, Fabio Facchinetti, Jerrie S Refuerzo, Sean C Blackwell, Baha M Sibai
BACKGROUND: Inositols (INOs) supplementation during pregnancy, specifically the combination of myo-inositol (MI) and D-chiro-inositol (DCI), has been reported to improve vascular parameters in women with gestational diabetes mellitus. We demonstrated previously that offspring born to pregnant mice lacking endothelial nitric oxide synthase (eNOS+/-) gene have hypertension (HTN) as adults and when fed high fat diet (HFD) develop a metabolic syndrome (MS) phenotype. OBJECTIVE: Our aim was to evaluate if INOs treatment in pregnancy complicated by MS improves the vascular and metabolic profile in mice offspring programmed in utero to develop HTN and MS...
December 3, 2018: American Journal of Obstetrics and Gynecology
Wai San Cheang, Wing Tak Wong, Li Wang, Chak Kwong Cheng, Chi Wai Lau, Ronald Chin Wan Ma, Aimin Xu, Nanping Wang, Yu Huang, Xiao Yu Tian
Sirtuin 1 (SIRT1) activation reduces oxidative stress, inhibits inflammatory responses, and retards cellular senescence in endothelial cells in mouse models of diabetes. However, whether SIRT1 also plays a protective role in vascular dysfunction of diabetic and obese mice is not fully characterized. Previous work showed that peroxisome proliferator-activated receptor δ (PPARδ) is beneficial in diabetic vascular dysfunction. Whether PPARδ is involved in the beneficial effect of SIRT1 on vascular endothelial function is unknown...
November 29, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Ying Shi, Xue Lv, Yanan Liu, Bochuan Li, Mingming Liu, Meng Yan, Yajin Liu, Qi Li, Xuejiao Zhang, Shuang He, Mason Zhu, Jinlong He, Yan Zhu, Yi Zhu, Ding Ai
Endothelial progenitor cell (EPC) dysfunction contributes to diabetes-induced delay in endothelium repair after vessel injury, prominently associated with diabetic cardiovascular complications such as neointima formation. ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol efflux to HDL, which may favorably affect EPC function. However, whether ABCG1 improves EPC function, especially in diabetes, remains unknown. Here we investigated the role of ABCG1 in EPCs by using Tie2-mediated ABCG1 transgenic (Tie2- ABCG1Tg ) mice...
December 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Kasavajhala V S K Prasad, Denghui Xing, Anireddy S N Reddy
Soil salinity, a significant problem in agriculture, severely limits the productivity of crop plants. Plants respond to and cope with salt stress by reprogramming gene expression via multiple signaling pathways that converge on transcription factors. To develop strategies to generate salt-tolerant crops, it is necessary to identify transcription factors that modulate salt stress responses in plants. In this study, we investigated the role of VOZ (VASCULAR PLANT ONE-ZINC FINGER PROTEIN) transcription factors (VOZs) in salt stress response...
November 23, 2018: International Journal of Molecular Sciences
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