Diana N. Krause

picture of Diana N. Krause

Adjunct Professor, Pharmacology
School of Medicine

PH.D., University of California, Los Angeles, 1977

Phone: (949) 824-7314
Fax: (949) 824-4855
Email: dnkrause@uci.edu

University of California, Irvine
Department of Pharmacology
350A Med Surge II
Mail Code: 4625
Irvine, CA 92697
Research Interests
Cerebral vascular pharmacology, hormonal regulation of brain circulation, stroke mechanisms, estrogen protection of mitochondria
Academic Distinctions
2001, UCI Chancellor’s Award for Excellence in (Mentoring) Undergraduate Research

2009, American Heart Association Harold and Henrietta Lee Award
Research Abstract
Our research has been focused on understanding how hormones affect blood vessels in the brain. The cerebral circulation is critical for normal brain function and vascular dysfunction contributes to pathological states such as stroke, cerebral edema and vascular dementia.

A major goal has been to determine the effects of the gonadal hormones, estrogen, progesterone and testosterone on cerebral blood vessels. Our findings are important contributions to understanding the impact of menopause, hormone replacement therapy and steroid abuse on the cerebral circulation. In addition, we are learning underlying reasons for the male-female difference in risk of cardiovascular disease and stroke.

We have found that both estrogen and testosterone alter the endothelial cells that line the lumen of cerebral blood vessels. Estrogen increases release of vasodilators such as nitric oxide and prostacyclin while testosterone increases vasoconstriction. We also find opposite effects of the hormones on vascular inflammation in the brain: estrogen decreases while testosterone increases induction of inflammatory markers. Specific hormone receptors are expressed in brain vessels that trigger both acute and chronic signaling pathways. Most recently we have discovered that estrogen has protective effects on vascular mitochondria that result in increased energy production while decreasing production of harmful free radicals.

Our experimental approach has been to study cerebral arteries and intracerebral microvessels that have been exposed to hormones either in vitro or under physiological conditions in vivo. We assess vascular contractility and biochemical changes to determine the hormonal impact on endothelial and smooth muscle function as well as on receptor and cell signaling pathways.
Recent Publications:

Edvinsson, L. and Krause, D.N., Eds. Cerebral Blood Flow and Metabolism, 2nd Edition, Lippincott, Williams & Wilkins, Philadelphia, PA, 2002.

Stirone, C, Duckles, SP, Krause, DN and Procaccio, V: Estrogen increases mitochondrial efficiency and reduces oxidative stress in cerebral blood vessels. Molecular Pharmacology 68:959-965, 2005.

Krause DN, Duckles SP and Pelligrino DP. Invited minireview: The influence of sex steroid hormones on cerebrovascular function. J. Appl. Physiol. 101:1252-1261, 2006.

Duckles SP, Krause DN, Stirone C and Procaccio V. Estrogen and mitochondria: A new paradigm for vascular protection? Molecular Interventions 6:26-35, 20

Sunday, L, Tran, MM, Krause, DN, and Duckles, SP: Estrogen and progestagens differentially modulate vascular proinflammatory factors. American Journal of Physiology: Endocrinology and Metabolism, 291: E261-E267, 2006.

Sunday L, Osuna C, Krause DN and Duckles, SP. Age alters cerebrovascular inflammation and effects of estrogen. Am. J. Physiol. Heart Circ. Physiol. 292:H2333-2340, 2007.

Gonzales RJ, Ansar S, Duckles SP and Krause DN. Androgenic/estrogenic balance in the male rat cerebral circulation: Metabolic enzymes and sex steroid receptors. J. Cereb. Blood Flow Metab. 27:1841-1852, 2007.

Duckles SP and Krause DN. Cerebrovascular effects of oestrogen: multiplicity of action. Clin. Exp. Pharmacol. Physiol. 34:801-808, 2007.

Razmara A, Krause DN, Duckles SP and Procaccio V. Estrogen suppresses brain mitochondrial oxidative stress in female and male rats. Brain Res. 1176:71-81, 2007.

Razmara A, Sunday L, Stirone C, Wang XB, Krause DN, Duckles SP, Procaccio V. Mitochondrial effects of estrogen are mediated by estrogen receptor alpha in brain endothelial cells. J Pharmacol Exp Ther 325: 782-790, 2008.

Gonzales, RJ, Duckles, SP and Krause, DN: Dihydrotestosterone stimulates cerebrovascular inflammation through NFkB, modulating contractile function, Journal of Cerebral Blood Flow and Metabolism, 29: 244-253, 2009.
Guo J, Krause DN, Horne J, Weiss JH, Li X, Duckles SP. Estrogen-receptor-mediated protection of cerebral endothelial cell viability and mitochondrial function after ischemic insult in vitro. J Cereb Blood Flow Metab. 30:545-554, 2010.

Dubocovich ML, Delagrange P, Krause DN, Sugden D, Cardinali DP, Olcese J. International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol Rev. 62:343-380, 2010.

Guo J, Duckles SP, Weiss JH, Li X, Krause DN. 17ß-Estradiol prevents cell death and mitochondrial dysfunction by an estrogen receptor-dependent mechanism in astrocytes after oxygen-glucose deprivation/reperfusion. Free Radic Biol Med. 52:2151-2160, 2012.

Kemper MF, Zhao Y, Duckles SP, Krause DN. Endogenous ovarian hormones affect mitochondrial efficiency in cerebral endothelium via distinct regulation of PGC-1 isoforms. J Cereb Blood Flow Metab. 33:122-128, 2013.

Ahnstedt H, Cao L, Krause DN, Warfvinge K, Säveland H, Nilsson OG, Edvinsson L. Male-female differences in upregulation of vasoconstrictor responses in human cerebral arteries. PLoS One. 8:e62698, 2013.

Kemper MF, Stirone C, Krause DN, Duckles SP, Procaccio V. Genomic and non-genomic regulation of PGC1 isoforms by estrogen to increase cerebral vascular mitochondrial biogenesis and reactive oxygen species protection. Eur J Pharmacol. 723:322-329, 2014.

Ahnstedt H, Mostajeran M, Blixt FW, Warfvinge K, Ansar S, Krause DN, Edvinsson L. U0126 attenuates cerebral vasoconstriction and improves long-term neurologic outcome after stroke in female rats. J Cereb Blood Flow Metab. 35:454-460, 2015.
Professional Societies
American Society for Pharmacology and Experimental Therapeutics
Society for Neuroscience
American Heart Association
International Society for Cerebral Blood Flow & Metabolism
Other Experience
Hedda Anderson Guest Professor of Pharmacology
University of Lund, Sweden 2011—pres

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