Dr Scott Mackenzie

Lecturer (Cardiovascular & Metabolic Health)

telephone: 01413302669
email: Scott.MacKenzie@glasgow.ac.uk

Rm C437, BHF Glasgow Cardiovascular Research Centre, 126 University Place, Glasgow, G12 8TA

Biography

My core research investigates the cardiovascular impact of the steroid hormones aldosterone and cortisol, particularly the regulation of their production by the adrenal gland. Loss of this tightly-controlled process has severe consequences for the vascular system, including hypertension, and to damage of organs including the heart and kidneys. Much of my work has focused on how common genetic variations leads to overproduction of these steroids, predisposing large sections of the population to high blood pressure, which often goes undiagnosed and untreated, despite the availability of effective treatments. To this end, I have contributed to several large-scale genetic studies identifying polymorphisms at steroidogenic loci that could aid diagnosis and therapeutic targeting of specific subtypes of hypertension. My work also includes investigation of the mechanisms by which these polymorphisms exert their effects, including studies of transcriptional activity, promoter binding, mRNA quantification and microRNA regulation. I am currently developing an interest in stress and its impact on cardiovascular disease through aldosterone secretion.

My research has a truly translational approach, encompassing laboratory analysis of isolated cells, investigation of tissue samples and full clinical studies. As an example of the latter, I am currently involved in the Europe-wide ENS@T-HT study, which is using ‘omics’ approaches to develop diagnostic signatures for various endocrine forms of hypertension. To this end, I am involved in analysing levels of circulating microRNAs in hypertensive patients recruited in Glasgow and throughout Europe. As well as developing improved procedures to more effectively diagnose patients with such conditions as Primary Aldosteronism or Cushing’s Disease, it is highly likely that this project will yield mechanistic insights into the regulation and action of aldosterone and cortisol in health and disease.
I have productive research projects with numerous colleagues within the University of Glasgow, while my past and present external collaborators include Professor John Connell at the University of Dundee, Dr Trevor Bushell at Strathclyde University, Professor Maria-Christina Zennaro at INSERM, Paris and Professor William Rainey at the University of Mississippi. I have received research funding from the European Union, the Chief Scientist Office and the British Heart Foundation and I am a former RCUK and Hypertension Trust Research Fellow. Such funding has enabled my colleagues, students and me to maintain an active record of publishing in prominent journals such as Circulation, Nature and Hypertension over the last 20 years.

I am active in various professional consortia and societies, including the Society for Endocrinology, where I have been a longstanding member elected to its Science Committee, co-convenor of its Adrenal and Cardiovascular Network and leader of its Career Development Workshop, which is the Society’s main initiative for promoting the early career researchers among its over 2,600 members. I am a reviewer for funding bodies including the Medical Research Council and British Heart Foundation, and for journals including Endocrinology, Clinical Endocrinology and Hypertension.

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Research interests

Our group’s core research investigates the production of the steroid hormones aldosterone and cortisol by the cortex of the adrenal gland. In particular, we wish to understand how genetic variation between individuals influences the regulation of these steroids’ production and how this results in high blood pressure. To this end, I have contributed to several large-scale genetic studies involving our main genes of interest, aldosterone synthase and 11β-hydroxylase. I am currently investigating whether polymorphisms in the 11β-hydroxylase gene result in its reduced expression.
As well as contributing to our group’s core studies of adrenocortical steroid production, many of my studies have examined the emerging area of extra-adrenal steroidogenesis, whereby tissues such as the brain and adipose tissue appear capable of producing low levels of aldosterone and cortisol. I have detected the aldosterone synthase and 11β-hydroxylase enzymes within brain tissue and demonstrated that their genes can be regulated within the brain independently of the adrenal gland. Current studies are investigating a link between cortisol production within the brain and Alzheimer’s disease. Other ongoing research includes the study of these genes’ production within heart tissue and fat tissue, in an attempt to better understand the processes underlying heart disease and obesity.
I have productive research projects with a number of national and international collaborators, including Dr Trevor Bushell at Strathclyde University, Professor Jonathan Seckl at Edinburgh University and Professor Celso Gomez-Sanchez at the University of Mississippi.

Research:

Publications

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Number of items: 41.

2022

Reel, P. S. et al. (2022) Machine learning for classification of hypertension subtypes using multi-omics: a multi-centre, retrospective, data-driven study. EBioMedicine, 84, 104276. (doi: 10.1016/j.ebiom.2022.104276) (PMID:36179553) (PMCID:PMC9520210)

Moudio, S. et al. (2022) Protease-activated receptor 2 activation induces behavioural changes associated with depression-like behaviour through microglial-independent modulation of inflammatory cytokines. Psychopharmacology, 239(1), pp. 229-242. (doi: 10.1007/s00213-021-06040-1) (PMID:34888704) (PMCID:PMC8770450)

Armignacco, R. et al. (2022) Whole blood methylome-derived features to discriminate endocrine hypertension. Clinical Epigenetics, 14, 142. (doi: 10.1186/s13148-022-01347-y) (PMID:36329530) (PMCID:PMC9635165)

2021

MacKenzie, S. M. , Saunders, H., van Kralingen, J. C., Robertson, S. , Riddell, A. , Zennaro, M.-C. and Davies, E. (2021) Circulating microRNAs as diagnostic markers in primary aldosteronism. Cancers, 13(21), 5312. (doi: 10.3390/cancers13215312) (PMCID:PMC8582381)

2019

MacKenzie, S. M. , Nguyen Dinh Cat, A., van Kralingen, J. and Davies, E. (2019) Aldosterone. In: Touyz, R. M. and Delles, C. (eds.) Textbook of Vascular Medicine. Springer: Cham, pp. 103-115. ISBN 9783030164805 (doi: 10.1007/978-3-030-16481-2_10)

MacKenzie, S. M. , Van Kralingen, J. C. and Davies, E. (2019) Regulation of aldosterone secretion. In: Litwack, G. (ed.) Aldosterone. Series: Vitamins and Hormones (109). Elsevier, pp. 241-263. ISBN 9780128177822 (doi: 10.1016/bs.vh.2018.07.001)

2018

McCarroll, C. S. et al. (2018) Runx1 deficiency protects against adverse cardiac remodeling after myocardial infarction. Circulation, 137(1), pp. 57-70. (doi: 10.1161/CIRCULATIONAHA.117.028911) (PMID:29030345) (PMCID:PMC5757664)

2017

Robertson, S., Diver, L. A., Alvarez-Madrazo, S., Livie, C., Ejaz, A., Fraser, R., Connell, J. M., MacKenzie, S. M. and Davies, E. (2017) Regulation of corticosteroidogenic genes by microRNAs. International Journal of Endocrinology, 2017, 2021903. (doi: 10.1155/2017/2021903) (PMID:28852406) (PMCID:PMC5568613)

MacKenzie, S. M. , Freel, M., Connell, J. M., Fraser, R. and Davies, E. (2017) ACTH and polymorphisms at steroidogenic loci as determinants of aldosterone secretion and blood pressure. International Journal of Molecular Sciences, 18(3), 579. (doi: 10.3390/ijms18030579) (PMID:28272372) (PMCID:PMC5372595)

MacKenzie, S. M. , Davies, E. and Alvarez-Madrazo, S. (2017) Analysis of the aldosterone synthase (CYP11B2) and 11β-hydroxylase (CYP11B1) genes. In: Touyz, R. M. and Schiffrin, E. L. (eds.) Hypertension: Methods and Protocols. Series: Methods in molecular biology (1527). Springer: New York, pp. 139-150. ISBN 9781493966233 (doi: 10.1007/978-1-4939-6625-7_11)

2016

Abulkassim, R., Brett, R., MacKenzie, S. M. and Bushell, T. J. (2016) Proteinase-activated receptor 2 is involved in the behavioural changes associated with sickness behaviour. Journal of Neuroimmunology, 295-96, pp. 139-147. (doi: 10.1016/j.jneuroim.2016.04.016) (PMID:27235359)

Diver, L. A. et al. (2016) Common polymorphisms at the CYP17A1 locus associate with steroid phenotype: support for blood pressure genome-wide association study signals at this locus. Hypertension, 67(4), pp. 724-732. (doi: 10.1161/HYPERTENSIONAHA.115.06925) (PMID:26902494) (PMCID:PMC4789491)

Horikoshi, M. et al. (2016) Genome-wide associations for birth weight and correlations with adult disease. Nature, 538(7624), pp. 248-252. (doi: 10.1038/nature19806) (PMID:27680694) (PMCID:PMC5164934)

2013

Robertson, S., MacKenzie, S. M. , Alvarez-Madrazo, S., Diver, L. A., Lin, J., Stewart, P. M., Fraser, R., Connell, J. M. and Davies, E. (2013) MicroRNA-24 is a novel regulator of aldosterone and cortisol production in the human adrenal cortex. Hypertension, 62(3), pp. 572-578. (doi: 10.1161/HYPERTENSIONAHA.113.01102) (PMID:23836801)

Alvarez-Madrazo, S. et al. (2013) Common polymorphisms in the CYP11B1 and CYP11B2 genes: evidence for a digenic influence on hypertension. Hypertension, 61(1), pp. 232-239. (doi: 10.1161/HYPERTENSIONAHA.112.200741)

2012

McManus, F., Sands, W., Diver, L., MacKenzie, S. M. , Fraser, R., Davies, E. and Connell, J. M. (2012) APEX1 regulation of aldosterone synthase gene transcription is disrupted by a common polymorphism in humans. Circulation Research, 111(2), pp. 212-219. (doi: 10.1161/CIRCRESAHA.111.262931)

MacKenzie, S. M. , Connell, J. M.C. and Davies, E. (2012) Non-adrenal synthesis of aldosterone: A reality check. Molecular and Cellular Endocrinology, 350(2), pp. 163-167. (doi: 10.1016/j.mce.2011.06.026)

2010

McNeilly, A. D. et al. (2010) Bile acids modulate glucocorticoid metabolism and the hypothalamic-pituitary-adrenal axis in obstructive jaundice. Journal of Hepatology, 52(5), pp. 705-711. (doi: 10.1016/j.jhep.2009.10.037)

2009

Reynolds, R. M., Walker, B. R., Phillips, D. I., Dennison, E. M., Fraser, R., MacKenzie, S. M., Davies, E. and Connell, J. M. (2009) Programming of hypertension: associations of plasma aldosterone in adult men and women with birthweight, cortisol, and blood pressure. Hypertension, 53(6), pp. 932-936. (doi: 10.1161/HYPERTENSIONAHA.109.129320)

McManus, F., MacKenzie, S.M. and Freel, E.M. (2009) Central mineralocorticoid receptors, sympathetic activity, and hypertension. Current Hypertension Reports, 11(3), pp. 224-230. (doi: 10.1007/s11906-009-0039-0)

Davies, E., MacKenzie, S. M., Freel, E. M., Alvarez-Madrazo, S., Fraser, R. and Connell, J. M.C. (2009) Altered corticosteroid biosynthesis in essential hypertension: a digenic phenomenon. Molecular and Cellular Endocrinology, 300(1-2), pp. 185-191. (doi: 10.1016/j.mce.2008.09.014)

Holloway, C.D. et al. (2009) Effects of genetic variation in the aldosterone synthase (CYP11B2) gene on enzyme function. Clinical Endocrinology, 70(3), pp. 363-371. (doi: 10.1111/j.1365-2265.2008.03383.x)

2008

Huda, S. S., MacKenzie, S. M., Sattar, N., Fraser, R., Connell, J. M. C. and Davies, E. (2008) Depot-specific steroidogenic gene transcription in human adipose tissue. Clinical Endocrinology, 69(6), pp. 848-854. (doi: 10.1111/j.1365-2265.2008.03262.x)

Connell, J. M.C., MacKenzie, S. M. , Freel, E. M., Fraser, R. and Davies, E. (2008) A lifetime of aldosterone excess: long-term consequences of altered regulation of aldosterone production for cardiovascular function. Endocrine Reviews, 29(2), pp. 133-154. (doi: 10.1210/er.2007-0030)

Ye, P., Kenyon, C. J., MacKenzie, S. M. , Nichol, K., Seckl, J. R., Fraser, R., Connell, J. M.C. and Davies, E. (2008) Effects of ACTH, dexamethasone, and adrenalectomy on 11 β-hydroxylase (CYP11B1) and aldosterone synthase(CYP11B2) gene expression in the rat central nervous system. Journal of Endocrinology, 196(2), pp. 305-311. (doi: 10.1677/JOE-07-0439)

MacKenzie, S. M. , Dewar, D. , Stewart, W. , Fraser, R., Connell, J. M. C. and Davies, E. (2008) The transcription of steroidogenic genes in the human cerebellum and hippocampus: a comparative survey of normal and Alzheimer's tissue. Journal of Endocrinology, 196(1), pp. 123-130. (doi: 10.1677/JOE-07-0427)

2007

Barr, M. et al. (2007) Polymorphic variation in the 11 beta-hydroxylase gene associates with reduced 11-hydroxylase efficiency. Hypertension, 49(1), pp. 113-119. (doi: 10.1161/01.HYP.0000249904.93940.7a)

2006

MacKenzie, S. M. and Connell, J. M.C. (2006) Hypertension and the expanding role of aldosterone. Current Hypertension Reports, 8(3), pp. 255-261. (doi: 10.1007/s11906-006-0059-y) (PMID:17147925)

Barr, M., MacKenzie, S. , Wilkinson, D., Holloway, C., Friel, E., Miller, S., MacDonald, T., Fraser, R., Connell, J. and Davies, E. (2006) Functional effects of genetic variants in the 11 beta-hydroxylase (CYP11B1) gene. Clinical Endocrinology, 65, pp. 816-825. (doi: 10.1111/j.1365-2265.2006.02673.x)

2005

Ye, P. et al. (2005) The aldosterone synthase (CYP11B2) and 11 beta-hydroxylase (CYP11B1) genes are not expressed in the rat heart. Endocrinology, 146(12), pp. 5287-5293. (doi: 10.1210/en.2005-0370) (PMID:16179417)

2004

Connell, J. M.C., Fraser, R., MacKenzie, S. M. , Friel, E. C., Ingram, M. C., Holloway, C. D. and Davies, E. (2004) The impact of polymorphisms in the gene encoding aldosterone synthase (CYP11B2) on steroid synthesis and blood pressure regulation. Molecular and Cellular Endocrinology, 217(1-2), pp. 243-247. (doi: 10.1016/j.mce.2003.10.025) (PMID:15134824)

Kennon, B., Ingram, M., Friel, E., Anderson, N., MacKenzie, S. , Davies, E. , Shakerdi, L., Wallace, A., Fraser, R. and Connell, J. (2004) Aldosterone synthase gene variation and adrenocortical response to sodium status, angiotensin II and ACTH in normal male subjects. Clinical Endocrinology, 61, pp. 174-181. (doi: 10.1111/j.1365-2265.2004.02073.x)

MacKenzie, S. , Molloy, R., O'Dwyer, P., Vella, M. and Young, I. (2004) Impact of video colonoscopy on stage and outcome of patients with symptomatic colorectal cancer. Surgical Endoscopy and Other Interventional Techniques, 18(8), pp. 1268-1271.

2003

Davies, E. and MacKenzie, S. M. (2003) Extra-adrenal production of corticosteroids. Clinical and Experimental Pharmacology and Physiology, 30(7), pp. 437-445. (doi: 10.1046/j.1440-1681.2003.03867.x) (PMID:12823256)

Connell, J., Fraser, R., MacKenzie, S. and Davies, E. (2003) Is altered adrenal steroid biosynthesis a key intermediate phenotype in hypertension? Hypertension, 41, pp. 993-999. (doi: 10.1161/01.HYP.0000064344.00173.44)

Drummond, I., Galloway, D., MacKenzie, S., Molloy, R., Norrie, J., O'Dwyer, P., Vella, M. and Walker, A. (2003) Randomized clinical trial comparing consultant-led or open access investigation for large bowel symptoms. British Journal of Surgery, 90(8), pp. 941-947.

Ye, P., Kenyon, C., MacKenzie, S. , Seckl, J., Fraser, R., Connell, J. and Davies, E. (2003) Regulation of aldosterone synthase gene expression in the rat adrenal gland and central nervous system by sodium and angiotensin II. Endocrinology, 144, pp. 3321-3328. (doi: 10.1210/en.2003-0109)

2002

MacKenzie, S. M. , Fraser, R., Connell, J. M.C. and Davies, E. (2002) Local renin-angiotensin systems and their interactions with extra-adrenal corticosteroid production. Journal of the Renin-Angiotensin-Aldosterone System, 3(4), pp. 214-221. (doi: 10.3317/jraas.2002.043) (PMID:12584665)

MacKenzie, S. , Lai, M., Clark, C., Fraser, R., Gomez-Sanchez, C., Seckl, J., Connell, J. and Davies, E. (2002) 11beta-hydroxylase and aldosterone synthase expression in fetal rat hippocampal neurons. Journal of Molecular Endocrinology, 29(3), pp. 319-325. (doi: 10.1677/jme.0.0290319)

2000

MacKenzie, S.M. , Clark, C.J., Fraser, R., Gomez-Sanchez, C.E., Connell, J. and Davies, E. (2000) Expression of 11 beta-hydroxylase and aldosterone synthase genes in the rat brain. Journal of Molecular Endocrinology, 24(3), pp. 321-328. (doi: 10.1677/jme.0.0240321) (PMID:10828825)

MacKenzie, S.M. , Clark, C.J., Ingram, M.C., Lai, M., Seckl, J., Gomez-Sanchez, C.E., Fraser, R., Connell, J.M.C. and Davies, E. (2000) Corticosteroid production by fetal rat hippocampal neurons. Endocrine Research, 26(4), pp. 531-535. (doi: 10.3109/07435800009048566) (PMID:11196425)

This list was generated on Wed Sep 20 15:54:22 2023 BST.

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