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Vikas Pathak, Robert Aris, Brian C Jensen, Wei Huang, Hubert James Ford
BACKGROUND: Plasma pro-BNP (brain natriuretic peptide) levels are often elevated in response to right ventricular (RV) volume and pressure overload, parameters potentially affected by exercise. Plasma pro-BNP levels change in association with long-term changes in pulmonary hemodynamics, thereby serving as a potential biomarker in pulmonary arterial hypertension (PAH). The 6-min Walk Test (6MWT) and pro-BNP level are often checked in a single office visit. There is no universal standard for measuring Pro-BNP levels relative to the timing of the 6MWT...
March 21, 2018: Lung
Claire Hudson, Tomomi E Kimura, Aparna Duggirala, Graciela B Sala-Newby, Andrew C Newby, Mark Bond
Vascular smooth muscle cell (VSMC) proliferation has been implicated in the development of restenosis after angioplasty, vein graft intimal thickening and atherogenesis. We investigated the mechanisms underlying positive and negative regulation of VSMC proliferation by the transcription factor cyclic AMP response element binding protein (CREB). Incubation with the cAMP elevating stimuli, adenosine, prostacyclin mimetics or low levels of forksolin activated CREB without changing CREB phosphorylation on serine-133 but induced nuclear translocation of the CREB co-factors CRTC-2 and CRTC-3...
March 20, 2018: Scientific Reports
Zachary R Smith, Bryan Kelly, Rana L Awdish, Sara Hegab
Treprostinil diolamine is the first oral dosage preparation of a prostacyclin analogue for use in treatment naive pulmonary arterial hypertension (PAH). This case series and review of the available literature describes the experience of patients with PAH receiving treprostinil by intravenous (IV), subcutaneous (SQ), or inhalation route who were transitioned to treprostinil diolamine. At our institution, 3 patients were transitioned to treprostinil diolamine who received treprostinil administered by each of the alternative routes: IV, SQ, and inhalation...
January 1, 2018: Journal of Pharmacy Practice
Kai-Lun Liang, Ping Fang, Qiu-Qiu Shi, Jie Su, Bo Li, Su-Hong Chen, Gui-Yuan Lv
This study aimed to investigate the antihypertensive effect and possible mechanism of Dendrobium officinale flos on hypertensive rats induced by high glucose and high fat compound alcohol. The hypertensive models were successfully made by high-glucose and high-fat diet, with gradient drinking for 4 weeks, and then divided into model control group, valsartan (5.7 mg·kg⁻¹) positive control group and D. officinale flos groups (3,1 g·kg⁻¹). After 6 weeks of treatment, the blood pressure of rats was measured regularly...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Chu Shan Tan, Mun Fei Yam
Previous studies have demonstrated that 3'-hydroxy-5,6,7,4'-tetramethoxyflavone (TMF) content in Orthosiphon stamineus fractions correlate with its vasorelaxation activity. Even with the availability of previous studies, there is still very little information on the vasorelaxation effect of TMF, and few scientific studies have been carried out. Therefore, the present study was designed to investigate the vasorelaxation activity and mechanism of action of the TMF. The vasorelaxation activity and the underlying mechanisms of TMF were evaluated on thoracic aortic rings isolated from Sprague Dawley rats...
March 19, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Stephanie Makhoul, Elena Walter, Oliver Pagel, Ulrich Walter, Albert Sickmann, Stepan Gambaryan, Albert Smolenski, René P Zahedi, Kerstin Jurk
Platelets are circulating sentinels of vascular integrity and are activated, inhibited, or modulated by multiple hormones, vasoactive substances or drugs. Endothelium- or drug-derived NO strongly inhibits platelet activation via activation of the soluble guanylate cyclase (sGC) and cGMP elevation, often in synergy with cAMP-elevation by prostacyclin. However, the molecular mechanisms and diversity of cGMP effects in platelets are poorly understood and sometimes controversial. Recently, we established the quantitative human platelet proteome, the iloprost/prostacyclin/cAMP/protein kinase A (PKA)-regulated phosphoproteome, and the interactions of the ADP- and iloprost/prostacyclin-affected phosphoproteome...
March 14, 2018: Nitric Oxide: Biology and Chemistry
Sonntana Seang, Prasit Pavasant, Chalida N Limjeerajarus
INTRODUCTION: Angiogenesis is a key determinant in dental pulp regeneration. Iloprost is a synthetic prostacyclin that promotes angiogenesis. A three-dimensional culture that mimics the in vivo condition has been used in tissue engineering. This study investigated the effect of iloprost on promoting dental pulp angiogenesis by using the tooth slice organ culture system. METHODS: Tooth slices with intact pulp tissue were cut from molars extracted from 12 patients...
March 14, 2018: Journal of Endodontics
D Valenzuela, F Moya, M Luco, J L Tapia
50 years ago, Northway described Broncopulmonary Dysplasia (BPD) in preterm infants exposed to mechanical ventilation. Since then, their survival has increased, nevertheless a "new BPD" has appeared and its incidence has not diminished. One of the characteristics of this pathology is the the abnormal vascular remodeling, which in its most severe expression is known as Pulmonary Hyper tension (PH); with an incidence of 17% in patients with BPD, which is proportional to the severity of the disease (33% in severe BPD), and as mortality factor (up to 48% 2-year mortality in PH-BPD)...
December 2017: Revista Chilena de Pediatría
Rasa Tamosiuniene, Olga Manouvakhova, Paul Mesange, Toshie Saito, Jin Qian, Mrinmoy Sanyal, Yu-Chun Lin, Linh P Nguyen, Amir Luria, Allen B Tu, Joshua M Sante, Marlene Rabinovitch, Desmond J Fitzgerald, Brian B Graham, Aida Habtezion, Norbert F Voelkel, Laure Aurelian, Mark R Nicolls
<u>Rationale:</u> Pulmonary arterial hypertension (PH) is a life-threatening condition associated with immune dysregulation and abnormal regulatory T cell (Treg) activity, but it is currently unknown whether and how abnormal Treg function differentially affects males and females. <u>Objective:</u> To evaluate whether and how Treg-deficiency differentially affects male and female rats in experimental PH. <u>Methods and Results:</u> Male and female athymic rnu/rnu rats, lacking Tregs, were treated with the vascular endothelial growth factor receptor-2 (VEGFR2) inhibitor SU5416 or chronic hypoxia and evaluated for PH; some animals underwent Treg immune reconstitution (IR) before SU5416 administration...
March 15, 2018: Circulation Research
Jingwen Xia, Li Yang, Liang Dong, Mengjie Niu, Shengli Zhang, Zhiwei Yang, Gulinuer Wumaier, Ying Li, Xiaomin Wei, Yi Gong, Ning Zhu, Shengqing Li
Prostacyclin receptor (IP) and peroxisome proliferator-activated receptor-gamma (PPARγ) are both potential targets for treatment of pulmonary arterial hypertension (PAH). Expression of IP and PPARγ decreases in PAH, suggesting that screening of dual agonists of IP and PPARγ might be an efficient method for drug discovery. Virtual screening (VS) of potential IP-PPARγ dual-targeting agonists was performed in the ZINC database. Ten of the identified compounds were further screened, and cefminox was found to dramatically inhibit growth of PASMCs with no obvious cytotoxicity...
2018: Frontiers in Pharmacology
Zhongjian Cheng, Xinggui Shen, Xiaohua Jiang, Huimin Shan, Maria Cimini, Pu Fang, Yong Ji, Joon Young Park, Konstantinos Drosatos, Xiaofeng Yang, Christopher G Kevil, Raj Kishore, Hong Wang
Insufficient hydrogen sulfide (H2 S) has been implicated in Type 2 diabetic mellitus (T2DM) and hyperhomocysteinemia (HHcy)-related cardiovascular complications. We investigated the role of H2 S in T2DM and HHcy-induced endothelial dysfunction in small mesenteric artery (SMA) of db/db mice fed a high methionine (HM) diet. HM diet (8 weeks) induced HHcy in both T2DM db/db mice and non-diabetic db/+ mice (total plasma Hcy: 48.4 and 31.3 µM, respectively), and aggravated the impaired endothelium-derived hyperpolarization factor (EDHF)-induced endothelium-dependent relaxation to acetylcholine (ACh), determined by the presence of eNOS inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) and prostacyclin (PGI2 ) inhibitor indomethacin (INDO), in SMA from db/db mice but not that from db/+ mice...
February 14, 2018: Redox Biology
Caterina Matucci-Cerinic, Vivek Nagaraja, Francesca Prignano, Bashar Kahaleh, Silvia Bellando-Randone
Raynaud's phenomenon (RP) is a functional vascular disorder involving extremities. In his practice, the dermatologist may frequently encounter RP which affects mainly women and is categorized into a primary benign form and a secondary form associated with different diseases (infections, drugs, autoimmune and vascular conditions, hematologic, rheumatologic and endocrinologic disorders). Still today, the differential diagnosis is a clinical challenge. Therefore, a careful history and a physical examination, together with laboratory tests and nailfold capillaroscopy are mandatory...
March 6, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Marilena Crescente, Laura Menke, Melissa V Chan, Paul C Armstrong, Timothy D Warner
Platelets are important players in thrombosis and haemostasis with their function being modulated by mediators in the blood and the vascular wall. Among these, eicosanoids can both stimulate or inhibit platelet reactivity. Platelet cyclooxygenase (COX)-1 generated thromboxane (TX) A2 is the primary prostanoid that stimulates platelet aggregation; its action is counter-balanced by prostaglandin (PG)I2 (prostacyclin), a product of vascular COX. PGD2 , PGE2 , 12- hydroxyeicosatraenoic acid (HETE) or 15-HETE, are other prostanoid modulators of platelet activity, but some also play a role in carcinogenesis...
March 7, 2018: British Journal of Pharmacology
Judit Konya, Ahmed Al Qaissi, Thozhukat Sathyapalan, Ramzi Ajjan, Leigh Madden, Khalid M Naseem, Andrew Thomas Garrett, Eric Kilpatrick, Stephen L Atkin
Aims: To determine if clotting, platelet, and endothelial function were affected by simulated short-haul commercial air flight conditions (SF) in participants with type 2 diabetes (T2DM) compared to controls. Methods: 10 participants with T2DM (7 females, 3 males) and 10 controls (3 females, 7 males) completed the study. Participants were randomized to either spend 2 h in an environmental chamber at sea level conditions (temperature: 23°C, oxygen concentration 21%, humidity 45%), or subject to a simulated 2-h simulated flight (SF: temperature: 23°C, oxygen concentration 15%, humidity 15%), and crossed over 7 days later...
2018: Frontiers in Endocrinology
María E Soto, Verónica Guarner-Lans, Karla Y Herrera-Morales, Israel Pérez-Torres
Marfan syndrome (MFS) is a pleiotropic genetic disease involving the cardiovascular system where a fibrillin-1 mutation is present. This mutation is associated with accelerated activation of transforming growth factor β (TGFβ1) which contributes to the formation of aneurysms in the root of the aorta. There is an imbalance in the synthesis of thromboxane A2 (TXA2 ) and prostacyclin, that is a consequence of a differential protein expression of the isoforms of cyclooxygenases (COXs), suggesting an alteration of arachidonic acid (AA) metabolism...
2018: Frontiers in Physiology
Rachel K Hopper, Yan Wang, Valerie DeMatteo, Ashley Santo, Steven M Kawut, Okan U Elci, Brian D Hanna, Laura Mercer-Rosa
Pulmonary hypertension (PH) causes significant morbidity and mortality in children due to right ventricular (RV) failure. We sought to determine the effect of prostacyclin analogues on RV function assessed by echocardiography in children with PH. We conducted a retrospective cohort study of children with PH treated with a prostacyclin analogue (epoprostenol or treprostinil) between January 2001 and August 2015 at our center. Data were collected before initiation of treatment (baseline) and at 1-3 and 6-12 months after...
April 2018: Pulmonary Circulation
Francesca Polverino, Bartolome R Celli, Caroline A Owen
Chronic obstructive pulmonary disease (COPD) is characterized by chronic expiratory airflow obstruction that is not fully reversible. COPD patients develop varying degrees of emphysema, small and large airway disease, and various co-morbidities. It has not been clear whether these co-morbidities share common underlying pathogenic processes with the pulmonary lesions. Early research into the pathogenesis of COPD focused on the contributions of injury to the extracellular matrix and pulmonary epithelial cells...
January 2018: Pulmonary Circulation
Tomohiko Ichikawa, Tetsuhiro Yamada, Alexander Treiber, Carmela Gnerre, Jérôme Segrestaa, Swen Seeland, Kiyoko Nonaka
1. The metabolism of the prostacyclin receptor agonist selexipag (NS-304; ACT-293987) and its active metabolite MRE-269 (ACT-333679) has been investigated in liver microsomes and hepatocytes of rats, dogs, and monkeys. MRE-269 formation is the main pathway of selexipag metabolism, irrespective of species. Some interspecies differences were evident for both compounds in terms of both metabolic turnover and metabolic profiles. The metabolism of MRE-269 was slower than that of selexipag in all three species. 2...
February 22, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Jane A Mitchell, Nicholas S Kirkby
Eicosanoids represent a diverse family of lipid mediators with fundamental roles in controlling physiology and disease. Within the eicosanoid super family are prostanoids, which are specifically derived from arachidonic acid by the enzyme cyclooxygenase (COX). COX has two isoforms; COX-1 and COX-2. COX-2 is the therapeutic target for the nonsteroidal anti-inflammatory drug (NSAID) class of pain medications. Of the prostanoids, prostacyclin, first discovered by Sir Professor John Vane in 1976, remains amongst the best studied and retains an impressive pedigree as one the bodies fundamental cardiovascular protective pathways...
February 21, 2018: British Journal of Pharmacology
José M Centeno, Luis Miranda-Gómez, Mikahela A López-Morales, Teresa Jover-Mengual, María C Burguete, Vannina G Marrachelli, María Castelló-Ruiz, Alicia Aliena-Valero, Enrique Alborch, Francisco J Miranda
Diabetic nephropathy is associated with increased risk of cardiovascular disease. B-type natriuretic peptide (BNP) plays an important role in cardiovascular pathophysiology and therapeutics. The aim of the present study was to investigate the influence of experimental diabetes on the mechanisms that regulate the relaxant response of the rabbit renal artery to BNP. Arterial relaxations to BNP were enhanced in diabetic rabbits. Indomethacin enhanced BNP-induced relaxation in control rabbits but showed no effect in diabetic rabbits...
February 21, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
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