A5012374119- Pulmonary Hypertension Research and Treatments
- MicroRNA in disease regulation
- Nitric Oxide and Endothelin Effects
- Connexins and lens biology
- Circular RNAs in diseases
- Renin-Angiotensin System Studies
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Eicosanoids and Hypertension Pharmacology
- High Altitude and Hypoxia
- Cardiovascular Function and Risk Factors
- Neuroscience of respiration and sleep
- Cancer-related molecular mechanisms research
- S100 Proteins and Annexins
- Neonatal Respiratory Health Research
- Heart Failure Treatment and Management
- Cardiovascular Issues in Pregnancy
- Phosphodiesterase function and regulation
- Organic and Inorganic Chemical Reactions
- Heat shock proteins research
- Neurotransmitter Receptor Influence on Behavior
- Cancer, Hypoxia, and Metabolism
- Apelin-related biomedical research
- Regulation of Appetite and Obesity
- Chemotherapy-induced cardiotoxicity and mitigation
- RNA modifications and cancer
Glasgow Caledonian University
2009-2025
Kagoshima University
2020
Brigham and Women's Hospital
2020
Harvard University
2020
Jackson and Tull (United States)
2020
Zero to Three
2020
Center for Clinical Research (United States)
2020
National Hospital Organization
2020
University of Glasgow
2004-2014
Addenbrooke's Hospital
2012-2014
MicroRNAs (miRNAs) are small noncoding RNAs that have the capacity to control protein production through binding "seed" sequences within a target mRNA. Each miRNA is capable of potentially controlling hundreds genes. The regulation miRNAs in lung during development pulmonary arterial hypertension (PAH) unknown.We screened profiles longitudinal and crossover design PAH caused by chronic hypoxia or monocrotaline rats. We identified reduced expression Dicer, involved processing, onset after...
Despite improved understanding of the underlying genetics, pulmonary arterial hypertension (PAH) remains a severe disease. Extensive remodeling small arteries, including proliferation artery smooth muscle cells (PASMCs), characterizes PAH. MicroRNAs (miRNAs) are noncoding RNAs that have been shown to play role in vascular remodeling.We assessed miR-145 PAH.We localized mouse lung muscle. Using quantitative PCR, we demonstrated increased expression wild-type mice exposed hypoxia. PAH was...
Background— Increased serotonin (5-hydroxytryptamine, 5-HT) transporter activity has been observed in human familial pulmonary hypertension. Methods and Results— We investigated hemodynamics the development of hypoxia-induced hypertension vascular remodeling mice overexpressing gene for 5-HT (5-HTT+ mice). Right ventricular pressure was elevated 3-fold normoxic 5-HTT+ compared with their wild-type controls. Hypoxia-induced increases right hypertrophy were also potentiated mice. 5-HTT–like...
Tryptophan hydroxylase 1 catalyzes the rate-limiting step in synthesis of serotonin periphery. Recently, it has been shown that expression tryptophan gene is increased lungs and pulmonary endothelial cells from patients with idiopathic arterial hypertension. Here we investigated effect genetic deletion on hypoxia-induced hypertension mice by measuring hemodynamics vascular remodeling before after 2 weeks hypoxia. In wild-type mice, hypoxia right ventricular pressure remodeling. These effects...
Idiopathic and familial forms of pulmonary arterial hypertension (PAH) predominantly affect females through an unknown mechanism. Activity the serotonin transporter (SERT) may modulate development PAH, mice overexpressing SERT (SERT+ mice) develop PAH severe hypoxia-induced PAH. In central nervous system, oestrogens influence activity system. Therefore, we examined gender on in SERT+ how this is modulated by female hormones. was assessed via measurement right ventricular systolic pressure...
Abstract Background Idiopathic and familial forms of pulmonary arterial hypertension (PAH) occur more frequently in women than men. However, the reason for this remains unknown. Both calcium binding protein S100A4/Mts1 (Mts1) its endogenous receptor (receptor advanced glycosylation end products; RAGE) have been implicated development PAH. We wished to investigate if Mts1/RAGE pathway may play a role gender bias associated with Methods investigated effects on PAH mice over-expressing Mts1...
Pulmonary endothelial cell apoptosis is a transient, yet defining pathogenic event integral to the onset of many pulmonary vascular diseases such as hypertension (PH). However, there paucity information concerning molecular pathway(s) that control arterial apoptosis. Here, we introduce axis when functionally active seems induce in vitro and PH vivo. In response apoptotic stimuli, human cells exhibited robust induction programmed death 4 (PDCD4)/caspase-3/apoptotic pathway was reversible by...
The incidence of pulmonary arterial hypertension secondary to the use indirect serotinergic agonists such as aminorex and dexfenfluramine led "serotonin hypothesis" hypertension; however, role serotonin in dexfenfluramine-induced remains controversial. Here, we used novel transgenic mice lacking peripheral (deficient tryptophan hydroxylase-1; Tph1(-/-) mice) or overexpressing gene for human transporter (SERT; SERT(+) investigate this further.Dexfenfluramine administration (5 mg x kg(-1)...
AimsPulmonary arterial hypertension (PAH) occurs more frequently in women than men. Oestrogen and the oestrogen-metabolising enzyme cytochrome P450 1B1 (CYP1B1) play a role development of PAH. Anorectic drugs such as dexfenfluramine (Dfen) have been associated with Dfen mediates PAH via serotonergic mechanism we shown serotonin to up-regulate expression CYP1B1 human pulmonary artery smooth muscle cells (PASMCs). Thus here assess Dfen-induced
Pulmonary arterial hypertension (PAH) occurs more frequently in women with mutations bone morphogenetic protein receptor type 2 (BMPR2) and dysfunctional BMPR2 signalling underpinning heritable PAH. We have previously shown that serotonin can uncover a pulmonary hypertensive phenotype BMPR2+/− mice oestrogen increase serotinergic human smooth muscle cells (hPASMCs). Hence, here we wished to characterize the expression of receptors (ERs) male female arteries examined influence on ERα...
Pulmonary arterial 5-hydroxytryptamine (serotonin) (5-HT) transporter (SERT)-, 5-HT receptor expression, and 5-HT-induced vasoconstriction can be increased in pulmonary hypertension. These variables were studied normoxic hypoxic Fawn-Hooded (FH) Sprague-Dawley (SD) rats. Furthermore, we compared the functional effects of SERT inhibitors antagonists against arteries. 5-HT<sub>1B</sub> expression was greater FH rat lungs than SD rats, as 5-HT-mediated vasoconstriction. The 5-HT<sub>2A</sub>...
Pulmonary arterial hypertension (PAH) is up to threefold more prevalent in women than men. Female mice overexpressing the serotonin transporter (SERT; SERT+ mice) exhibit PAH and exaggerated hypoxia-induced PAH, whereas male remain unaffected. To further investigate these sex differences, microarray analysis was performed pulmonary arteries of normoxic chronically hypoxic female mice. Quantitative RT-PCR employed for validation data. In relevant groups, immunoblotting genes interest (CEBPβ,...
AimsA mechanism for co-operation between the serotonin (5-hydroxytryptamine, 5-HT) transporter and 5-HT1B receptor in mediating pulmonary artery vasoconstriction proliferation of smooth muscle cells has been demonstrated vitro. Here we determine, first time, vivo effects a combined receptor/serotonin antagonist (LY393558) with respect to development arterial hypertension (PAH) its vitro human (hPASMCs) derived from idiopathic PAH (IPAH) patients.
While the 5-HT and Rho-kinase (ROCK) pathways have been implicated in development of pulmonary arterial hypertension (PAH), nature any interactions between them remain unclear. This study investigated a role for ROCK 5-HT-regulated proliferative responses lung fibroblasts vivo vitro.PAH was examined mice over-expressing human transporters (SERT+), from which artery (PFs) were isolated to assess expression. In vitro analysis signalling employed CCL39 hamster fibroblasts.ROCK inhibition...
Pulmonary hypertension (PH) is a complex condition characterized by pulmonary artery constriction and vascular remodeling. Connexin 43 (Cx43), involved in cellular communication, may play role PH development. Cx43 heterozygous (Cx43+/−) mice show partial protection against hypoxia-induced remodeling, with prior research highlighting its rat fibroblast (PAF) proliferation migration. However, inhibiting compromise nitric oxide (NO)-mediated relaxation. This study evaluated the effects of on...
Pulmonary arterial hypertension (PAH) is a chronic condition characterized by vascular remodeling and increased vaso-reactivity. PAH more common in females than males (~3:1). Connexin (Cx)43 has been shown to be involved cellular communication within the pulmonary vasculature. Therefore, we investigated role of Cx43 reactivity using heterozygous (Cx43+/−) mice 37,43Gap27, which pharmacological inhibitor Cx37 Cx43. Contraction relaxation responses were studied intra-lobar arteries (IPAs)...
Pulmonary hypertension (PH) is a disease associated with vasoconstriction and remodelling of the pulmonary vasculature. artery fibroblasts (PAFs) play an important role in hypoxic-induced remodelling. Connexin 43 (Cx43) involved cellular communication regulation Using both vitro vivo models PH, aims this study were to (i) investigate Cx43 proliferation migration rat PAFs (rPAFs) smooth muscle cells (rPASMCs) (ii) determine whether expression dysregulated sugen5416/hypoxic model PH. The was...
<i>Background:</i> We hypothesised that the potential protective effects of endothelial ET<sub>B</sub> are important in limiting pulmonary vascular muscularisation, vasoconstriction and development arterial hypertension response to hypoxia. <i>Methods:</i> EC-specific knockout mice (EC ET<sub>B</sub><sup>–/–</sup>) control (ET<sub>B</sub><sup>f/f</sup>) were subjected hypobaric hypoxic (10%...
MicroRNAs are small noncoding RNAs involved in the regulation of gene expression and have recently been implicated development pulmonary arterial hypertension (PAH). Previous work has established that miR-451 is upregulated rodent models PAH. The role circulation unknown. We therefore sought to assess involvement Silencing was performed vivo using knockout mice an anti-miR targeting mature rats. Coupled with exposure hypoxia, indices PAH were assessed. effect modulating on human artery...