Corticosteroid Hormones in Cardiovascular Disease

High blood pressure is the major risk factor for coronary disease, heart failure and stroke, which are estimated to be responsible for 7 million excess deaths each year worldwide.  Of the various factors contributing to blood pressure homeostatis, the steroids aldosterone and cortisol play a crucial role.  These hormones are made in the adrenal gland by the enzymes aldosterone synthase and 11β-hydroxylase and are encoded by the CYP11B2 and CYP11B1 genes respectively.  Using a translational research approach integrating basic molecular biology, in vitro cell biology and human investigations, our studies have advanced our understanding of adrenal steroid synthesis regulation and the contribution of steroids to cardiovascular dysfunction. 

Some of our projects are linked below:

• Clinical Studies of Corticosteroids in Cardiovascular Disease
• Genetic and Epigenetic Regulation of CYP11B1 and CYP11B2
• Structure of Aldosterone Synthase and 11β-Hydroxylase  
• Role of co-factors in corticosteroid enzyme activity  
• Corticosteroid Production

Publications:

1. Barr M, MacKenzie SM, Friel EC, Holloway CD, Wilkinson DM, Brain NJ, Ingram MC, Fraser R, Brown M, Samani NJ, Caulfield M, Munroe PB, Farrall M, Webster J, Clayton D, Dominiczak AF, Connell JM, Davies E.  Polymorphic variation in the 11beta-hydroxylase gene associates with reduced 11-hydroxylase efficiency.  Hypertension 2007;49:113-19.
2. Connell JM, MacKenzie SM, Friel EM, Fraser R, Davies E. A Lifetime of Aldosterone Excess: Long-Term Consequences of Altered Regulation of Aldosterone Production for Cardiovascular Function. Endocr Rev 2008;29:133-54.
3. Freel EM, Ingram M, Friel EC, Fraser R, Brown M, Samani NJ, Caulfield M, Munroe P, Farrall M, Webster J, Clayton D, Dominiczak AF, Davies E, Connell JM.  Phenotypic consequences of variation across the aldosterone synthase and 11-beta hydroxylase locus in a hypertensive cohort: data from the MRC BRIGHT Study. Clin Endocrinol (Oxf) 2007;67:832-38.
4. MacKenzie SM, Dewar D, Stewart W, Fraser R, Connell JM, Davies E. The transcription of steroidogenic genes in the human cerebellum and hippocampus: a comparative survey of normal and Alzheimer's tissue. J Endocrinol 2008;196:123-30.
5. Reynolds RM, Walker BR, Philips DI, Dennison EM, Fraser R, Mackenzie SM, Davies E, Connell JM. Programming of hypertension: associations of plasma aldosterone in adult men and women with birthweight, cortisol, and blood pressure. Hypertension 2009;53:932-36.