McNeish, Alister - University of Reading

研究领域

Cardiovascular disease is the leading cause of mortality in the UK and in our aging population the incidence of cardiovascular disease is increasing. Therefore there is a pressing need for new and better treatments for these diseases. My main focus is on vascular pharmacology. In particular how the endothelial cells, which line inside of blood vessels, communicate and modulate the degree of constriction of the smooth muscle cells that form the wall of blood vessels. Understanding these processes help us develop new strategies for regulating blood flow and blood pressure; perhaps leading to new treatments for cardiovascular diseases. My work falls roughly in to four inter-related themes: a) Regulation of calcium-activated potassium channels (KCa) found in the endothelium. These channels play a critical role in endothelium derived hyperpolarization (EDH) mediated responses and regulation of blood pressure/flow. This theme also encompasses how such regulation affects EDH responses. b) Characterisation and elucidation of the mechanisms that underlie the endothelium dependent hyperpolarization, particularly in the cerebral vasculature with a particular focus on the role of fatty acid derived metabolites (including omega-3 fatty acids) and reactive oxygen species on these responses. c) The study of "food factors" like omega-3 fatty acids (fish oils), flavonoids and polyphenolic acids on vascular and endothelial cell function in heath and disease. d) The role of the endothelium in regulating spontaneous vasoconstrictor tone (myogenic tone) in smooth muscle cells. This has implications on vasomotion (a coordinated oscillatory relaxation and constriction of blood vessels) and vasospasm (uncontrolled vasoconstriction associated with strokes and heart attacks).

近期论文

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Onetti, Y., Dantas, A. Y., Perez, B., McNeish, A. J., Vila, E. and Jimenez-Altyayo, F. (2016) Peroxynitrate formed during a transient episode of brain ischemia increases endothelium-derived hyperpolarization-type dilations in thromboxane/prostaglandin receptor stimulated rat cerebral arteries. Acta Physiologica. ISSN 1748-1716 doi: 10.1111/apha.12809 (In Press) Gauthier, K. M., Campbell, W. B. and McNeish, A. J. (2014) Regulation of KCa2.3 andendothelium-dependent hyperpolarization (EDH) in the rat middle cerebral artery: the role of lipoxygenase metabolites and isoprostanes. PeerJ, 2. e414. ISSN 2167-8359 doi: 10.7717/peerj.414 McNeish, A., Roux, B. T., Aylett, S.-B. , Van Den Brink, A. M. and Cottrell, G. S. (2012) Endosomal proteolysis regulates calcitonin gene-related peptide responses in mesenteric arteries. British Journal of Pharmacology, 167 (8). pp. 1679-1690. ISSN 1476-5381 doi: 10.1111/j.1476-5381.2012.02129.x McNeish, A. J., Altayo-Jimenez, F., Cottrell, G. S. and Garland, C. J. (2012) Statins and selective inhibition of Rho kinase protect small conductance calcium-activated potassium channel function (KCa2.3) in cerebral arteries. PLoS ONE, 7 (10). e46735. ISSN 1932-6203 doi: 10.1371/journal.pone.0046735 McNeish, A., Altayo-Jimenez, F. and Garland, C. J. (2010) Evidence both L-type and non-L-type voltage-dependent calcium channels contribute to cerebral artery vasospasm following loss of NO in the rat. Vascular Pharmacology, 53 (3-4). pp. 151-159. ISSN 1537-1891 doi: 10.1016/j.vph.2010.06.002 Yuill, K. H., McNeish, A., Kansui, Y., Garland, C. J. and Dora , K. A. (2010) Nitric oxide suppresses cerebral vasomotion by sGC-independent effects on ryanodine receptors and voltage-gated calcium channels. Journal of Vascular Research, 47 (2). pp. 93-107. ISSN 1018-1172 doi: 10.1159/000235964 Dora, K. A., Gallagher, N. T., McNeish, A. and Garland, C. J. (2008) Modulation of endothelial cell KCa3.1 Channels during endothelium-derived hyperpolarizing factor signaling in mesenteric resistance arteries. Circulation Research, 102 (10). pp. 1427-1255. ISSN 0009-7330 doi: 10.1161/CIRCRESAHA.108.172379