Dr. Alexander W. Krug
Integrating Hormonal Signaling into Cardiovascular Disease - From Basic Mechanisms to Clinical Implications
Previous and current research
Classically, the steroid hormone aldosterone is synthesised in the zona glomerulosa of the adrenal gland. According to the traditional view aldosterone binds to specific mineralocorticoid receptors located in the cytosol of target epithelial cells and a specific pattern of proteins is induced. In the consequence water and electrolyte homeostasis and hence blood pressure is regulated. This demonstrates the importance of aldosterone in the pathogenesis of hypertension.Furthermore, recent years have unvealed that aldosterone, besides its well known way of action as mineralocorticoid, causes cardiovascular disease like left ventricular fibrosis leading to cardiac death in patients with chronic heart failure or after myocardial infarction. Recent studies have demonstrated major therapeutic benefits of mineralocorticoid receptor antagonism in cardiac failure. Moreover, aldosterone was described to promote vascular inflammation and fibrosis as well as endothelial dysfunction.
There is also evidence that aldosterone is produced in extra-adrenal tissues like the heart or the vasculature and might act localy in a autocrine or paracrine way. Although these findings remain controversial they help to explain, at least in part, the pathological aldosterone effects. But the exact pathophysiological mechanisms whereby aldosterone induces these adverse cardiovascular effects remain only poorly understood.
This figure gives an overview of aldosterone secretion mechanisms as well as physiological and pathological aldosterone actions.
Future prospects and goals
- What are the basic mechanisms of alternative (“non-genomic”) aldosterone action? Can these alternative aldosterone actions help to explain the adverse aldosterone effects in the cardiovascular system? (In cooperation with Prof. M. Gekle, Department of Physiology, University of Würzburg)
- Which role does aldosterone play in the pathogenesis of atherosclerosis?
- Based on a thorough understanding of the alternative aldosterone actions we aim to develop new and better treatments for these syndroms.
- Krug, A. W., and Ehrhart-Bornstein M. (2005): Newly Discovered Endocrine functions of white adipose tissue. Possible relevance in obesity-related diseases Cell Mol Lifesciences. 62 (2005) 1359–1362
- Grossmann C, Benesic A, Krug A.W. , Freudinger R, Mildenberger S, Gassner B, Gekle M. (2005): Human mineralocorticoid receptor expression renders cells responsive for nongenotropic aldosterone actions Mol Endocrinology 19: 1697–1710.
- Krug AW, Grossmann C, Schuster C, Freudinger R, Mildenberger S, Govindan MV and Gekle M (2003): Aldosterone Stimulates Epidermal Growth Factor Receptor Expression. J Biol Chem Oct 2003 31; 278, (44): 43060–43066.
- Krug, AW, Schuster C., Gassner B., Mildenberger S., Troppmair J. and Gekle M. (2002): Human epidermal growth factor receptor-1 expression renders Chinese hamster ovary cells sensitive to alternative aldosterone signaling. J Biol Chem. 2002 Nov 29;277(48):45892-7
1995-2001: Medical School at the University of Würzburg and at the University of Rochester, USA2001MD at the University of Würzburg
2001-2003: Training in Basic Research, Department of Physio-logy, University of WürzburgFunding by “Senator Kurt und Inge Schuster” FoundationResearch Award from the German Kidney Foundation (Deutsche Nierenstiftung)
2003: Diploma in Health Care Management (Gesundheitsökonom ebs)
2003-2004: Resident at the University of Bonn and at the German Diabetes Center, Clinical Division, University of Düsseldorf.Funding by the Research Commission of the University of Düsseldorf.Research grant from the Jühling Foundation, German Diabetes Society (Deutsche Diabetes Gesellschaft)
since 2004: University of Dresden, Medical Clinic III.Research grant from Ernst und Berta Grimmke Foundation.Funding by Glaxo-Smith Kline GmbH.