Imperial College London

MrAlexAinscough

Faculty of MedicineNational Heart & Lung Institute

Research Postgraduate
 
 
 
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alex.ainscough14

 
 
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ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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5 results found

Hislop A, Ainscough A, Wojciak-Stothard B, 2020, Endothelial Cells and Endothelium, Encyclopedia of Respiratory Medicine

Journal article

Sindi HA, Russomanno G, Satta S, Abdul-Salam VB, Jo KB, Qazi-Chaudhry B, Ainscough AJ, Szulcek R, Bogaard HJ, Morgan CC, Pullamsetti SS, Alzaydi MM, Rhodes CJ, Piva R, Eichstaedt CA, Grunig E, Wilkins MR, Wojciak-Stothard Bet 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

Journal article

Sindi H, Russomanno G, Satta S, Abdul Saalam V, Kyeong Beom J, Qazi-Chaudhry B, Ainscough A, Szulcek R, Bogaard HJ, Morgan C, Pullamsetti S, Alzaydi M, Rhodes C, Piva R, Eichstaedt C, GrĂ¼nig E, Wilkins M, Wojciak-Stothard Bet 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.

Journal article

Paulose Nadappuram B, Cadinu P, Barik A, Ainscough A, Devine M, Kang M, Gonzalez-Garcia J, Kittler J, Willison K, Vilar Compte R, Actis P, Wojciak-Stothard B, Oh S-H, Ivanov A, Edel JBet al., 2019, Nanoscale tweezers for single-cell biopsies, Nature Nanotechnology, Vol: 14, Pages: 80-88, ISSN: 1748-3387

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.

Journal article

Aldabbous L, Abdul-Salam V, McKinnon T, Duluc L, Pepke-Zaba J, Southwood M, Ainscough AJ, Hadinnapola C, Wilkins M, Toshner M, Wojciak-Stothard Bet 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

Journal article

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