80 results found
Alzaydi M, Abdul Salam V, Whitwell H, et al., 2023, Intracellular chloride channels regulate endothelial metabolic reprogramming in pulmonary arterial hypertension, American Journal of Respiratory Cell and Molecular Biology, Vol: 63, Pages: 103-115, ISSN: 1044-1549
Mitochondrial fission and a metabolic switch from oxidative phosphorylation to glycolysis are key features of vascular pathology in pulmonary arterial hypertension (PAH) and are associated with exuberant endothelial proliferation and apoptosis. The underlying mechanisms are poorly understood. We describe the contribution of two intracellular chloride channel proteins CLIC1 and CLIC4, both highly expressed in PAH and cancer, to mitochondrial dysfunction and energy metabolism in PAH endothelium. Pathological overexpression of CLIC proteins induces mitochondrial fragmentation, inhibits mitochondrial cristae formation and induces metabolic shift towards glycolysis in human pulmonary artery endothelial cells, consistent with changes observed in patient-derived cells. Interactions of CLIC proteins with structural components of the inner mitochondrial membrane offer mechanistic insights. Endothelial CLIC4 excision and mitofusin 2 supplementation have protective effects in human PAH cells and pre-clinical PAH. This study is first to demonstrate the key role of endothelial intracellular chloride channels in the regulation of mitochondrial structure, biogenesis, and metabolic reprogramming in expression of the PAH phenotype.
Wojciak-Stothard B, Ainscough AJ, Smith TJ, et al., 2022, An organ-on-chip model of pulmonary arterial hypertension identifies a BMPR2-SOX17-prostacyclin signalling axis, Communications Biology, Vol: 5, Pages: 1-15, ISSN: 2399-3642
Pulmonary arterial hypertension (PAH) is an unmet clinical need. The lack of models of human disease is a key obstacle to drug development. We present a biomimetic model of pulmonary arterial endothelial-smooth muscle cell interactions in PAH, combining natural and induced bone morphogenetic protein receptor 2 (BMPR2) dysfunction with hypoxia to induce smooth muscle activation and proliferation, which is responsive to drug treatment. BMPR2- and oxygenation-specific changes in endothelial and smooth muscle gene expression, consistent with observations made in genomic and biochemical studies of PAH, enable insights into underlying disease pathways and mechanisms of drug response. The model captures key changes in the pulmonary endothelial phenotype that are essential for the induction of SMC remodelling, including a BMPR2-SOX17-prostacyclin signalling axis and offers an easily accessible approach for researchers to study pulmonary vascular remodelling and advance drug development in PAH.
Beaumont J, Aboagye E, Wojciak-Stothard B, et al., 2022, Apelinergic signalling in hepatocellular carcinoma (HCC): A new therapeutic treatment option., Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Beaumont J, Aboagye E, Wojciak-Stothard B, et al., 2022, Apelinergic signalling in hepatocellular carcinoma (HCC): A new therapeutic treatment option, Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Wojciak-Stothard B, Ainscough A, Smith T, et al., 2021, A MICROFLUIDIC CHIP FOR PULMONARY ARTERIAL HYPERTENSION
<jats:title>Abstract</jats:title> <jats:p>Pulmonary arterial hypertension (PAH) is an unmet clinical need. The lack of a disease model representative of the human condition is a key obstacle to the development of new treatments. Here we present a model of PAH, based on a biomimetic pulmonary artery (PA)-on-a-chip, that permits the study of the molecular and functional changes in human pulmonary vascular endothelial and smooth muscle cells in response to triggers of the disease and their response to drugs. We combine natural or induced BMPR2 dysfunction with hypoxia in vascular endothelial cells to trigger smooth muscle activation and proliferation and relate accompanying transcriptomic changes in affected cells to functional effects. Changes in gene expression consistent with observations made in genomic and biochemical studies of the human disease enable insights into underlying disease pathways and mechanisms of drug response. The model offers a novel, promising and more easily accessible approach for researchers to study pulmonary vascular remodelling and advance drug development in PAH.</jats:p>
Nicoleau S, Fellows A, Wojciak-Stothard B, 2021, Role of Kr & uuml;ppel-like factors in pulmonary arterial hypertension, INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, Vol: 134, ISSN: 1357-2725
Russomanno G, Jo KB, Abdul-Salam V, et al., 2021, miR-150-PTPMT1-cardiolipin signaling in pulmonary arterial hypertension, Molecular Therapy : Nucleic Acids, Vol: 23, Pages: 142-153, ISSN: 2162-2531
Circulating levels of endothelial miR-150 are reduced in pulmonary arterial hypertension (PAH) and act as an independent predictor of patient survival, but links between endothelial miR-150 and vascular dysfunction are not well understood. We studied the effects of endothelial miR-150 supplementation and inhibition in PAH mice and cells from patients with idiopathic PAH. The role of selected mediators of miR-150 identified by RNA sequencing was evaluated in vitro and in vivo. Endothelium-targeted miR-150 delivery prevented the disease in Sugen/hypoxia mice, while endothelial knockdown of miR-150 had adverse effects. miR-150 target genes revealed significant associations with PAH pathways, including proliferation, inflammation, and phospholipid signaling, with PTEN-like mitochondrial phosphatase (PTPMT1) most markedly altered. PTPMT1 reduced inflammation and apoptosis and improved mitochondrial function in human pulmonary endothelial cells and blood-derived endothelial colony-forming cells from idiopathic PAH. Beneficial effects of miR-150 in vitro and in vivo were linked with PTPMT1-dependent biosynthesis of mitochondrial phospholipid cardiolipin and reduced expression of pro-apoptotic, pro-inflammatory, and pro-fibrotic genes, including c-MYB, NOTCH3, transforming growth factor β (TGF-β), and Col1a1. In conclusion, we are the first to show that miR-150 supplementation attenuates pulmonary endothelial damage induced by vascular stresses and may be considered as a potential therapeutic strategy in PAH.
Medvedev R, Sanchez-Alonso JL, Alvarez-Laviada A, et al., 2021, Nanoscale Study of Calcium Handling Remodeling in Right Ventricular Cardiomyocytes Following Pulmonary Hypertension, HYPERTENSION, Vol: 77, Pages: 605-616, ISSN: 0194-911X
Nicoleau S, Wojciak-Stothard B, 2020, Beyond thrombosis: the role of platelets in pulmonary hypertension, SciMedicine Journal, Vol: 2, Pages: 243-271, ISSN: 2704-9833
Pulmonary Hypertension (PH) is a multifactorial and lethal disease, characterised by elevated pulmonary arterial pressure and progressive right heart failure. PH pathobiology rests on four pillars: vascular remodelling, vasoconstriction, inflammation and thrombosis. While vascular and inflammatory cells have been the focus of PH research over the past decades, platelets have received relatively less attention, despite their associations with key pathophysiological processes of the disease. Platelets contain a wide range of vasoactive, inflammatory and pro-thrombotic mediators, likely to promote PH development and progression. There is currently no cure for PH, and platelet-associated pathways may help identify new therapeutic strategies. This review summarises available evidence on the role of platelets in different forms of PH, and comments on the current state of platelet-targeting therapies. It also describes the latest advances in the in vitro technologies that enable exploration of platelet function under dynamic and physiologically relevant conditions.
Hislop A, Ainscough A, Wojciak-Stothard B, 2020, Endothelial Cells and Endothelium, Encyclopedia of Respiratory Medicine
Lou H, Wojciak-Stothard B, Ruseva MM, et al., 2020, Autoantibody-dependent amplification of inflammation in SLE, Cell Death and Disease, Vol: 11, ISSN: 2041-4889
Anti-double stranded DNA antibodies (anti-dsDNA) are a hallmark of SLE but their role in disease pathogenesis is not fully resolved. Anti-dsDNA in serum are highly heterogeneous therefore in this study, we aimed to dissect the functional specificities of anti-dsDNA using a panel of human monoclonal antibodies (humAbs) generated from patients with active lupus nephritis. A total of 46 ANA reactive humAbs were isolated and divided into four broad classes based on their reactivity to histones, DNA and Crithidia. Functional analysis indicated that one subclass of antibodies bound strongly to decondensed DNA areas in neutrophil extracellular traps (NETs) and protected NETs from nuclease digestion, similar to the sera from active SLE patients. In addition, these anti-dsDNA antibodies could stimulate type I interferon responses in mononuclear phagocytic cells, or NF-kB activity in endothelial cells, by uptake of NETs-anti-NETs immune complexes and subsequently trigging inflammatory responses in an Fc-gamma receptor (Fcg-R)-dependant manner. Together our data suggest that only a subset of anti-dsDNA antibodies is capable to amplify inflammatory responses by deposit in the nephritic kidney in vivo, protecting NETs digestion as well as uptake of NETs immune complexes into Fcg-R-expressing cells in vitro.
Sindi HA, Russomanno G, Satta S, et al., 2020, Therapeutic potential of KLF2-induced exosomal microRNAs in pulmonary hypertension (vol 33, pg 631, 2020), Nature Communications, Vol: 11, Pages: 1-1, ISSN: 2041-1723
Sindi H, Russomanno G, Satta S, et al., 2020, Therapeutic potential of KLF2 induced exosomal microRNAs in pulmonary hypertension, Nature Communications, Vol: 11, ISSN: 2041-1723
Pulmonary arterial hypertension (PAH) is a severe disorder of lung vasculature that causes right heart failure. Homeostatic effects of flow-activated transcription factor Krüppel-like factor 2 (KLF2) are compromised in PAH. Here we show that KLF2-induced exosomal microRNAs, miR-181a-5p and miR-324-5p act together to attenuate pulmonary vascular remodeling and that their actions are mediated by Notch4 and ETS1 and other key regulators of vascular homeostasis. Expressions of KLF2, miR-181a-5p and miR-324-5p are reduced, while levels of their target genes are elevated in pre-clinical PAH, idiopathic PAH and heritable PAH with missense p.H288Y KLF2 mutation. Therapeutic supplementation of miR-181a-5p and miR-324-5p reduces proliferative and angiogenic responses in patient-derived cells and attenuates disease progression in PAH mice.This study shows that reduced KLF2 signaling is a common feature of human PAH and highlights the potential therapeutic role of KLF2-regulated exosomal miRNAs in PAH and other diseases associated with vascular remodelling.
Storck Saha E, Morales Sanfrutos J, Serwa R, et al., 2019, Dual chemical probes enable quantitative system-wide analysis of protein prenylation and prenylation dynamics, Nature Chemistry, Vol: 11, Pages: 552-561, ISSN: 1755-4330
Post-translational farnesylation or geranylgeranylation at a C-terminal cysteine residue regulates the localization and function of over 100 proteins, including the Ras isoforms, and is a therapeutic target in diseases including cancer and infection. Here, we report global and selective profiling of prenylated proteins in living cells enabled by the development of isoprenoid analogues YnF and YnGG in combination with quantitative chemical proteomics. Eighty prenylated proteins were identified in a single human cell line, 64 for the first time at endogenous abundance without metabolic perturbation. We further demonstrate that YnF and YnGG enable direct identification of post-translationally processed prenylated peptides, proteome-wide quantitative analysis of prenylation dynamics and alternative prenylation in response to four different prenyltransferase inhibitors, and quantification of defective Rab prenylation in a model of the retinal degenerative disease choroideremia.
Much of the functionality of multicellular systems arises from the spatial organization and dynamic behaviours within and between cells. Current single-cell genomic methods only provide a transcriptional ‘snapshot’ of individual cells. The real-time analysis and perturbation of living cells would generate a step change in single-cell analysis. Here we describe minimally invasive nanotweezers that can be spatially controlled to extract samples from living cells with single-molecule precision. They consist of two closely spaced electrodes with gaps as small as 10–20 nm, which can be used for the dielectrophoretic trapping of DNA and proteins. Aside from trapping single molecules, we also extract nucleic acids for gene expression analysis from living cells without affecting their viability. Finally, we report on the trapping and extraction of a single mitochondrion. This work bridges the gap between single-molecule/organelle manipulation and cell biology and can ultimately enable a better understanding of living cells.
Abdul-Salam V, Russomanno G, Chien-Nien C, et al., 2019, CLIC4/Arf6 pathway – a new lead in BMPRII inhibition in pulmonary hypertension, Circulation Research, Vol: 124, Pages: 52-65, ISSN: 0009-7330
Rationale:Increased expression of CLIC4 (chloride intracellular channel 4) is a feature of endothelial dysfunction in pulmonary arterial hypertension, but its role in disease pathology is not fully understood.Objective:To identify CLIC4 effectors and evaluate strategies targeting CLIC4 signaling in pulmonary hypertension.Methods and Results:Proteomic analysis of CLIC4-interacting proteins in human pulmonary artery endothelial cells identified regulators of endosomal trafficking, including Arf6 (ADP ribosylation factor 6) GTPase activating proteins and clathrin, while CLIC4 overexpression affected protein regulators of vesicular trafficking, lysosomal function, and inflammation. CLIC4 reduced BMPRII (bone morphogenetic protein receptor II) expression and signaling as a result of Arf6-mediated reduction in gyrating clathrin and increased lysosomal targeting of the receptor. BMPRII expression was restored by Arf6 siRNA, Arf inhibitor Sec7 inhibitor H3 (SecinH3), and inhibitors of clathrin-mediated endocytosis but was unaffected by chloride channel inhibitor, indanyloxyacetic acid 94 or Arf1 siRNA. The effects of CLIC4 on NF-κB (nuclear factor-kappa B), HIF (hypoxia-inducible factor), and angiogenic response were prevented by Arf6 siRNA and SecinH3. Sugen/hypoxia mice and monocrotaline rats showed elevated expression of CLIC4, activation of Arf6 and NF-κB, and reduced expression of BMPRII in the lung. These changes were established early during disease development. Lung endothelium–targeted delivery of CLIC4 siRNA or treatment with SecinH3 attenuated the disease, reduced CLIC4/Arf activation, and restored BMPRII expression in the lung. Endothelial colony–forming cells from idiopathic pulmonary hypertensive patients showed upregulation of CLIC4 expression and Arf6 activity, suggesting potential importance of this pathway in the human condition.Conclusions:Arf6 is a novel effector of CLIC4 and a new therapeutic target in pulmonary hypertension.
Sindi H, Russomanno G, Wojciak-Stothard B, 2017, Anti-Inflammatory And Anti-Apoptotic Effects Of KLF2-Induced MIRS In Pulmonary Vascular Endothelium, 2nd Joint Meeting of the European-Society-for-Microcirculation (ESM) and European-Vascular-Biology-Organisation (EVBO), Publisher: KARGER, Pages: 72-72, ISSN: 1018-1172
Russomanno G, Osman A, Stothard BW, 2017, Mir-150 as a Regulator of Endothelial Function in Pulmonary Arterial Hypertension, 2nd Joint Meeting of the European-Society-for-Microcirculation (ESM) and European-Vascular-Biology-Organisation (EVBO), Publisher: KARGER, Pages: 41-42, ISSN: 1018-1172
Duluc L, Ahmetaj-Shala B, Mitchell J, et al., 2017, Tipifarnib prevents development of hypoxia-induced pulmonary hypertension, Cardiovascular Research, Vol: 113, Pages: 276-287, ISSN: 1755-3245
Aims.RhoB plays a key role in the pathogenesis of hypoxia-induced pulmonary hypertension. Farnesylated RhoB promotes growth responses in cancer cells and we investigated whether inhibition of protein farnesylation will have a protective effect. Methods and Results.The analysis of lung tissues from rodent models and pulmonary hypertensive patientsshowed increased levels of protein farnesylation. Oral farnesyltransferase inhibitor tipifarnib prevented development of hypoxia-induced pulmonary hypertension in mice. Tipifarnib reduced hypoxia-induced vascular cell proliferation, increased endothelium-dependent vasodilatation and reduced vasoconstriction of intrapulmonary arteries without affecting cell viability. Protective effects of tipifarnib were associated with inhibition of Ras and RhoB, actin depolymerisation and increased eNOS expression in vitroand in vivo. Farnesylated-only RhoB (F-RhoB) increased proliferative responses in cultured pulmonary vascular cells, mimicking the effects of hypoxia, while both geranylgeranylated-only RhoB (GG-RhoB) and tipifarnib had an inhibitory effect. Label-free proteomics linked F-RhoB with cell survival, activation of cell cycle and mitochondrial biogenesis. Hypoxia increased and tipifarnib reduced the levels of F-RhoB-regulated proteins in the lung, reinforcing the importance of RhoB as a signalling mediator.Unlike simvastatin, tipifarnib did not increase the expression levels of Rho proteins.Conclusions.Our study demonstrates the importance of protein farnesylation in pulmonary vascular remodeling and provides a rationale for selective targeting of this pathway in pulmonary hypertension.
Aldabbous L, Abdul-Salam V, McKinnon T, et al., 2016, Neutrophil Extracellular Traps Promote Angiogenesis: Evidence From Vascular Pathology in Pulmonary Hypertension., Arteriosclerosis, Thrombosis, and Vascular Biology, Vol: 36, Pages: 2078-2087, ISSN: 1079-5642
OBJECTIVE: Inflammation and dysregulated angiogenesis are features of endothelial dysfunction in pulmonary hypertension. Neutrophil extracellular traps (NETs), produced by dying neutrophils, contribute to pathogenesis of numerous vascular disorders but their role in pulmonary hypertension has not been studied. We sought evidence of (NETs) formation in pulmonary hypertension and investigated the effect of NETs on endothelial function. APPROACH AND RESULTS: Plasma and lung tissues of patients with pulmonary hypertension were analyzed for NET markers. The effects of NETs on endothelial function were studied in vitro and in vivo. Patients with chronic thromboembolic pulmonary hypertension and idiopathic pulmonary hypertension showed elevated plasma levels of DNA, neutrophil elastase, and myeloperoxidase. NET-forming neutrophils and extensive areas of NETosis were found in the occlusive plexiform lesions and vascularized intrapulmonary thrombi. NETs induced nuclear factor κB-dependent endothelial angiogenesis in vitro and increased vascularization of matrigel plugs in vivo. Angiogenic responses were associated with increased release of matrix metalloproteinase-9, heparin-binding EGF-like growth factor, latency-associated peptide of the transforming growth factor β1, and urokinase-type plasminogen activator, accompanied by increased endothelial permeability and cell motility. NETs-induced responses depended on myeloperoxidase/H2O2-dependent activation of Toll-like receptor 4/nuclear factor κB signaling. NETs stimulated the release of endothelin-1 in HPAECs and stimulated pulmonary smooth muscle cell proliferation in vitro. CONCLUSIONS: We are the first to implicate NETs in angiogenesis and provide a functional link between NETs and inflammatory angiogenesis in vitro and in vivo. We demonstrate the potential pathological relevance of this in 2 diseases of disordered vascular homeostasis, pulmonary arterial hypertension and chronic thromboembolic pulmonary
Mohamed NA, Ahmetaj-Shala B, Duluc L, et al., 2016, A New NO-Releasing Nanoformulation for the Treatment of Pulmonary Arterial Hypertension., Journal of Cardiovascular Translational Research, Vol: 9, Pages: 162-164, ISSN: 1937-5395
Pulmonary arterial hypertension (PAH) is a chronic and progressive disease which continues to carry an unacceptably high mortality and morbidity. The nitric oxide (NO) pathway has been implicated in the pathophysiology and progression of the disease. Its extremely short half-life and systemic effects have hampered the clinical use of NO in PAH. In an attempt to circumvent these major limitations, we have developed a new NO-nanomedicine formulation. The formulation was based on hydrogel-like polymeric composite NO-releasing nanoparticles (NO-RP). The kinetics of NO release from the NO-RP showed a peak at about 120 min followed by a sustained release for over 8 h. The NO-RP did not affect the viability or inflammation responses of endothelial cells. The NO-RP produced concentration-dependent relaxations of pulmonary arteries in mice with PAH induced by hypoxia. In conclusion, NO-RP drugs could considerably enhance the therapeutic potential of NO therapy for PAH.
Belik D, Tsang H, Wharton J, et al., 2016, Endothelium-derived microparticles from chronically thromboembolic pulmonary hypertensive patients facilitate endothelial angiogenesis., Journal of Biomedical Science, Vol: 23, ISSN: 1423-0127
BACKGROUND: Increased circulating levels of endoglin(+) endothelial microparticles (EMPs) have been identified in several cardiovascular disorders, related to severity. Endoglin is an auxilary receptor for transforming growth factor β (TGF-β) important in the regulation of vascular structure. RESULTS: We quantified the number of microparticles in plasma of six patients with chronic thromboembolic pulmonary hypertension (CTEPH) and age- and sex-matched pulmonary embolic (PE) and healthy controls and investigated the role of microparticle endoglin in the regulation of pulmonary endothelial function in vitro. Results show significantly increased levels of endoglin(+) EMPs in CTEPH plasma, compared to healthy and disease controls. Co-culture of human pulmonary endothelial cells with CTEPH microparticles increased intracellular levels of endoglin and enhanced TGF-β-induced angiogenesis and Smad1,5,8 phosphorylation in cells, without affecting BMPRII expression. In an in vitro model, we generated endothelium-derived MPs with enforced membrane localization of endoglin. Co-culture of these MPs with endothelial cells increased cellular endoglin content, improved cell survival and stimulated angiogenesis in a manner similar to the effects induced by overexpressed protein. CONCLUSIONS: Increased generation of endoglin(+) EMPs in CTEPH is likely to represent a protective mechanism supporting endothelial cell survival and angiogenesis, set to counteract the effects of vascular occlusion and endothelial damage.
Iannone L, Zhao L, Dubois O, et al., 2014, miR-21/DDAH1 pathway regulates pulmonary vascular responses to hypoxia, BIOCHEMICAL JOURNAL, Vol: 462, Pages: 103-112, ISSN: 0264-6021
Wojciak-Stothard B, Abdul-Salam VB, Lao KH, et al., 2014, Aberrant chloride intracellular channel 4 expression contributes to endothelial dysfunction in pulmonary arterial hypertension, Circulation, Vol: 129, Pages: 1770-1780, ISSN: 0009-7322
Background—Chloride intracellular channel 4 (CLIC4) is highly expressed in the endothelium of remodeled pulmonary vessels and plexiform lesions of patients with pulmonary arterial hypertension. CLIC4 regulates vasculogenesis through endothelial tube formation. Aberrant CLIC4 expression may contribute to the vascular pathology of pulmonary arterial hypertension.Methods and Results—CLIC4 protein expression was increased in plasma and blood-derived endothelial cells from patients with idiopathic pulmonary arterial hypertension and in the pulmonary vascular endothelium of 3 rat models of pulmonary hypertension. CLIC4 gene deletion markedly attenuated the development of chronic hypoxia-induced pulmonary hypertension in mice. Adenoviral overexpression of CLIC4 in cultured human pulmonary artery endothelial cells compromised pulmonary endothelial barrier function and enhanced their survival and angiogenic capacity, whereas CLIC4 shRNA had an inhibitory effect. Similarly, inhibition of CLIC4 expression in blood-derived endothelial cells from patients with idiopathic pulmonary arterial hypertension attenuated the abnormal angiogenic behavior that characterizes these cells. The mechanism of CLIC4 effects involves p65-mediated activation of nuclear factor-κB, followed by stabilization of hypoxia-inducible factor-1α and increased downstream production of vascular endothelial growth factor and endothelin-1.Conclusion—Increased CLIC4 expression is an early manifestation and mediator of endothelial dysfunction in pulmonary hypertension.
Duluc L, Wojciak-Stothard B, 2014, Rho GTPases in the regulation of pulmonary vascular barrier function, CELL AND TISSUE RESEARCH, Vol: 355, Pages: 675-685, ISSN: 0302-766X
Iannone L, Leiper J, Zhao L, et al., 2014, Ddah1 Regulates Pulmonary Vascular Responses To Hypoxia Via Mir-21, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 189, ISSN: 1073-449X
Tsang H, Leiper J, Lao KH, et al., 2013, Role of asymmetric methylarginine and connexin 43 in the regulation of pulmonary endothelial function, PULMONARY CIRCULATION, Vol: 3, Pages: 675-691, ISSN: 2045-8932
Storck EM, Wojciak-Stothard B, 2013, Rho GTPases in pulmonary vascular dysfunction, VASCULAR PHARMACOLOGY, Vol: 58, Pages: 202-210, ISSN: 1537-1891
Rhodes CJ, Wharton J, Boon RA, et al., 2013, Reduced microRNA-150 is associated with poor survival in pulmonary arterial hypertension., American Journal of Respiratory and Critical Care Medicine, Vol: 187, Pages: 294-302
MicroRNAs (miRNAs or miRs) are implicated in the pathogenesis of various cardiovascular diseases, including pulmonary arterial hypertension (PAH).
Tsang HH, Leiper J, Lao KH, et al., 2012, The Role of ADMA Metabolism in the Regulation of Human Pulmonary Endothelial Cell Function, CIRCULATION, Vol: 126, ISSN: 0009-7322
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.