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Stephen Moss, Vasanta Subramanian, K Ravi Acharya
Neprilysin is a transmembrane M13 zinc metalloprotease responsible for the degradation of several biologically active peptides including insulin, enkephalin, substance P, bradykinin, endothelin-1, neurotensin and amyloid-β. The protein has received attention for its role in modulating blood pressure responses with its inhibition producing an antihypertensive response. To date, several inhibitor bound crystal structures of the human neprilysin extracellular domain have been determined, but, a structure free of bound inhibitor or substrate has yet to be reported...
June 12, 2018: Journal of Structural Biology
Hye Eun Yoon, Yaeni Kim, Sang Dong Kim, Jin Kyoung Oh, Yong-An Chung, Seok Joon Shin, Chul Woo Yang, Suk Min Seo
BACKGROUND Inflammatory activity of the artery can be assessed by measuring 18F-fluorodeoxyglucose (18F-FDG) uptake with positron emission tomography computed tomography (PET/CT). Improvement in vascular function after renal transplantation has been reported, but no studies have used 18F-FDG PET/CT to examine the changes in vascular inflammation. This study investigated the changes in the inflammatory activity in the carotid artery after renal transplantation in patients with chronic kidney disease (CKD). MATERIAL AND METHODS 18F-FDG PET/CT was performed before and at 4 months after transplantation...
June 15, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Rulin Zhuang, Jinfu Wu, Fang Lin, Lu Han, Xiaoting Liang, Qingshu Meng, Yuyu Jiang, Zhulin Wang, Aixue Yue, Yuying Gu, Huimin Fan, Xiaohui Zhou, Zhongmin Liu
Pulmonary hypertension (PH) due to left heart disease (LHD) is a common condition associated with significant morbidity. It contributes to the elevation of pulmonary vascular resistance and mean pulmonary pressure, eventually leading to heart failure and even mortality. The present study aimed to explore the potential efficacy of late and long‑term treatment with a Rho‑kinase (ROCK) signaling inhibitor, namely fasudil, in a rat model of end‑stage PH‑LHD. The PH‑LHD model was established by supracoronary aortic banding, and the effect of fasudil treatment on the progression of PH‑LHD was monitored...
June 13, 2018: International Journal of Molecular Medicine
Jan Polak, Naresh M Punjabi, Larissa A Shimoda
Obstructive sleep apnea (OSA) is associated with insulin resistance (IR) and glucose intolerance. Elevated endothelin-1 (ET-1) levels have been observed in OSA patients and in mice exposed to intermittent hypoxia (IH). We examined whether pharmacological blockade of type A and type B ET-1 receptors (ETA and ETB ) would ameliorate glucose intolerance and IR in mice exposed to IH. Subcutaneously implanted pumps delivered BQ-123 (ETA antagonist; 200 nmol/kg/day), BQ-788 (ETB antagonist; 200 nmol/kg/day) or vehicle (saline or propyleneglycol [PG]) for 14 days in C57BL6/J mice (10/group)...
2018: Frontiers in Endocrinology
Fares Ould-Brahim, Sailendra Nath Sarma, Charvi Syal, Kevin Jiaqi Lu, Matthew Seegobin, Anthony Carter, Matthew S Jeffers, Carole Doré, William Stanford, Dale Corbett, Jing Wang
While transplantation of hiPSC-derived neural stem cells (hiPSC-NSCs) shows therapeutic potential in animal stroke models, major concerns for translating hiPSC therapy to the clinic are efficacy and safety. Therefore, there is a demand to develop an optimal strategy to enhance the engraftment and regenerative capacity of transplanted hiPSC-NSCs in order to produce fully differentiated neural cells to replace lost brain tissues. Metformin, an FDA approved drug, is an optimal neuroregenerative agent that not only promotes NSC proliferation but also drives NSC towards differentiation...
June 12, 2018: Stem Cells and Development
Nungki Anggorowati, Ahmad Ghozali, Irianiwati Widodo, Dwi Cahyani Ratna Sari, Muhammad Mansyur Romi, Nur Arfian
Background: Heparanase and endothelin-1/endothelin A receptor (ET-1/ETA R) expressions increase in cancer. This condition enhances tumor progression and correlates with poor survival. Limited data are documented regarding the role of heparanase and ET-1/ETA R in epithelial ovarian cancer (EOC). We sought to characterize the correlation between heparanase and ET-1/ETA R in EOC. Methods: Thirty patients with benign and malignant ovarian neoplasms were recruited in this study...
May 2018: Iranian Journal of Medical Sciences
Krasimir Kostov, Lyudmila Halacheva
Arterial hypertension is a disease with a complex pathogenesis. Despite considerable knowledge about this socially significant disease, the role of magnesium deficiency (MgD) as a risk factor is not fully understood. Magnesium is a natural calcium antagonist. It potentiates the production of local vasodilator mediators (prostacyclin and nitric oxide) and alters vascular responses to a variety of vasoactive substances (endothelin-1, angiotensin II, and catecholamines). MgD stimulates the production of aldosterone and potentiates vascular inflammatory response, while expression/activity of various antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase) and the levels of important antioxidants (vitamin C, vitamin E, and selenium) are decreased...
June 11, 2018: International Journal of Molecular Sciences
Wei Yuan, Zhen-Xi Li, Cheng-Long Zhao, Tian-Hui Hou, Si-Wang Hu, Wei-Bo Liu, Feng-Lai Yuan, Jian-Ru Xiao
BACKGROUND: Context: Endothelin-1 (ET-1) is an inflammatory mediator associated with cartilage endplate (CEP) degeneration in the intervertebral disc. SOX9 is down-regulated during CEP degeneration, along with its targets, collagen II and aggrecan. Wnt/β-catenin signaling is associated with CEP degeneration and a downstream target of SOX9; however, the precise mechanism of CEP degeneration and the role of ET-1 are largely unknown. PURPOSE: The purpose of the study was to evaluate the influence of the endothelin A receptor antagonist, BQ-123, on ET-1-induced effects on cartilaginous endplate cells (CECs) associated with CEP degeneration via the Wnt/β-catenin signaling pathway...
June 7, 2018: Spine Journal: Official Journal of the North American Spine Society
Craig A Nash, Loren M Brown, Sundeep Malik, Xiaodong Cheng, Alan V Smrcka
In cardiac myocytes activation of an exchange factor activated by cAMP (Epac) leads to activation of phospholipase Cε (PLCε)-dependent hydrolysis of phosphatidylinositol 4-phosphate (PI4P) in the Golgi apparatus a process critical for development of cardiac hypertrophy. Here we show that β-adrenergic receptor (βAR) stimulation does not stimulate this pathway in the presence of the broad spectrum phosphodiesterase (PDE) inhibitor IBMX, but selective PDE3 inhibition revealed βAR-dependent PI4P depletion...
June 6, 2018: Journal of Molecular and Cellular Cardiology
Silvia Di Monaco, Adrien Georges, Jean-Philippe Lengelé, Miikka Vikkula, Alexandre Persu
Fibromuscular Dysplasia (FMD) is &ldquo;an idiopathic, segmental, non-atherosclerotic and non-inflammatory disease of the musculature of arterial walls, leading to stenosis of small and medium-sized arteries&rdquo; (Persu, et al; 2014). FMD can lead to hypertension, arterial dissections, subarachnoid haemorrhage, stroke or mesenteric ischemia. The pathophysiology of the disease remains elusive. While familial cases are rare (<5%) in contemporary FMD registries, there is evidence in favour of the existence of multiple genetic factors involved in this vascular disease...
May 21, 2018: International Journal of Molecular Sciences
Mariana Villegas-Romero, Vicente Castrejón-Téllez, Israel Pérez-Torres, María Esther Rubio-Ruiz, Elizabeth Carreón-Torres, Eulises Díaz-Díaz, Leonardo Del Valle-Mondragón, Verónica Guarner-Lans
Adverse conditions during early developmental stages permanently modify the metabolic function of organisms through epigenetic changes. Exposure to high sugar diets during gestation and/or lactation affects susceptibility to metabolic syndrome or hypertension in adulthood. The effect of a high sugar diet for shorter time lapses remains unclear. Here we studied the effect of short-term sucrose ingestion near weaning (postnatal days 12 and 28) (STS) and its effect after long-term ingestion, for a period of seven months (LTS) in rats...
June 6, 2018: Nutrients
Sandosh Padmanabhan, Alisha Aman, Anna F Dominiczak
PURPOSE OF REVIEW: Hypertension is recognised as the biggest contributor to the global burden of disease, but it is controlled in less than a fifth of patients worldwide, despite being relatively easy to detect and the availability of inexpensive safe generic drugs. Blood pressure is regulated by a complex network of physiologic pathways with currently available drugs targeting key receptors or enzymes in the top pathways. Major advances in the dissection of both monogenic and polygenic determinants of blood pressure regulation and variation have not resulted in rapid translation of these discoveries into clinical applications or precision medicine...
June 7, 2018: Current Hypertension Reports
Shuxiang Wang, Arash Azarfar, YaJing Wang, Zhijun Cao, Quangui Shi, Shengli Li
Objective: This study was conducted to investigate hematological and vasodilator characteristics for high altitude acclimatization in Holstein heifers ascended to high altitude. Methods: Holstein heifers resided at low altitude (LH; Beijing, China 43 meter), and Holstein heifers ascended to high altitude (Lhasa city, Tibet; 3,658 meter) after one year exposure including hypoxia acclimated Holstein heifers (AH; with mean pulmonary arterial pressure mPAP < 41 mmHg) and Holstein heifers affected by high altitude pulmonary hypertension (HAPH; with mPAP > 49 mmHg) and crossbred cattle (CB; Holstein × Tibet cattle) born and resided in Tibet were selected to compare parameters of blood gas, blood cells and vasodilators...
May 31, 2018: Asian-Australasian Journal of Animal Sciences
Basma Milad Aloud, Pema Raj, Jason McCallum, Chris Kirby, Xavier Lieben Louis, Fahmida Jahan, Liping Yu, Brett Hiebert, Todd A Duhamel, Jeffrey T Wigle, Heather Blewett, Thomas Netticadan
The present study investigated the effects of cyanidin 3-O-glucoside (C3G) in cardiomyocytes (CM) and fibroblasts exposed to endothelin 1 (ET1), as well as in the spontaneously hypertensive rat (SHR) model, alone or in combination with hydrochlorothiazide (HCT). Adult rat CM and cardiac fibroblasts (CF) were pretreated with C3G and co-incubated with ET1 (10-7 M) for 24 hours. Five-week-old male SHR and their normotensive controls, Wistar-Kyoto rats (WKY), received one of 4 treatments via oral gavage daily for 15 weeks: (1) water (control); (2) C3G (10 mg per kg per day); (3) HCT (10 mg per kg per day); (4) C3G + HCT (10 mg per kg per day each)...
June 7, 2018: Food & Function
William Rosenblum
Endothelium dependent responses were first demonstrated 40 years ago in the aorta. Since then extensive research has been conducted in vitro using conductance vessels and materials derived from them. However the microcirculation controls blood flow to vital organs and has been the focus of in vivo studies of endothelium dependent dilation beginning immediately after the first in vitro report. Initial in vivo studies employed a light/dye technique for selectively damaging the endothelium to unequivocally prove, in vivo, the existence of endothelium dependent dilation and in the microvasculature...
June 6, 2018: Acta Physiologica
Caroline Sunggip, Kakeru Shimoda, Sayaka Oda, Tomohiro Tanaka, Kazuhiro Nishiyama, Supachoke Mangmool, Akiyuki Nishimura, Takuro Numaga-Tomita, Motohiro Nishida
Cardiac hypertrophy, induced by neurohumoral factors, including angiotensin II and endothelin-1, is a major predisposing factor for heart failure. These ligands can induce hypertrophic growth of neonatal rat cardiomyocytes (NRCMs) mainly through Ca2+ -dependent calcineurin/nuclear factor of activated T cell (NFAT) signaling pathways activated by diacylglycerol-activated transient receptor potential canonical 3 and 6 (TRPC3/6) heteromultimer channels. Although extracellular nucleotide, adenosine 5'-triphosphate (ATP), is also known as most potent Ca2+ -mobilizing ligand that acts on purinergic receptors, ATP never induces cardiomyocyte hypertrophy...
2018: Frontiers in Pharmacology
Suping Zhang, Qian Huang, Qiaoling Wang, Qin Wang, Xiaoyun Cao, Liang Zhao, Nan Xu, Zhengbing Zhuge, Jianhua Mao, Xiaodong Fu, Ruisheng Liu, Christopher S Wilcox, Andreas Patzak, Lingli Li, En Yin Lai
BACKGROUND/AIMS: Canonical Wnt signaling is involved in oxidative stress, vasculopathy and diabetes mellitus but its role in diabetic renal microvascular dysfunction is unclear. We tested the hypothesis that enhanced canonical Wnt signaling in renal afferent arterioles from diabetic mice increases reactive oxygen species (ROS) and contractions to endothelin-1 (ET-1). METHODS: Streptozotocin-induced diabetes or control C57Bl/6 mice received vehicle or sulindac (40 mg·kg-1·day-1) to block Wnt signaling for 4 weeks...
May 30, 2018: Kidney & Blood Pressure Research
Arthur D Moes, David Severs, Koen Verdonk, Nils van der Lubbe, Robert Zietse, A H J Danser, Ewout J Hoorn
Inflammation is increasingly recognized as a driver of hypertension. Both genetic and pharmacological inhibition of B and T cells attenuates most forms of experimental hypertension. Accordingly, the immunosuppressive drug mycophenolate mofetil (MMF) reduces blood pressure in the deoxycorticosterone acetate (DOCA-) salt model. However, the mechanisms by which MMF prevent hypertension in the DOCA-salt model remain unclear. Recent studies indicate that immunosuppression can inhibit sodium transporter activity in the kidney, but its effect on vascular tone is not well characterized...
2018: Frontiers in Physiology
Jia-Mei Yang, Ru Zhou, Min Zhang, Huan-Ran Tan, Jian-Qiang Yu
BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, leading to right ventricular failure and death. Recent studies have suggested that chronic inflammatory processes are involved in the pathogenesis of PAH. Several studies have demonstrated that betaine possesses outstanding anti-inflammatory effects. However, whether betaine exerts protective effects on PAH by inhibiting inflammatory responses in the lungs needs to be explored...
May 26, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Pei-Ling Hsu, Yung-Ching Lin, Hao Ni, Fan-E Mo
Ganoderma mushrooms, used in traditional Chinese medicine to promote health and longevity, have become widely accepted as herbal supplements. Ganoderma lucidum (GL), a commonly seen ganoderma species, is commercially cultivated under controlled conditions for more consistent chemical composition. The medicinal properties of GL are attributable to its antioxidant and anti-inflammatory activities. We intended to assess the effect of GL in atherosclerosis, an arterial condition associated with chronic oxidative stress and inflammation, using a carotid-artery-ligation mouse model...
2018: Oxidative Medicine and Cellular Longevity
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