Diana N. Krause
Adjunct Professor, Department of Pharmaceutical Sciences
School of Pharmacy & Pharmaceutical Sciences
School of Pharmacy & Pharmaceutical Sciences
Co-Director, Master of Science in Pharmacology Degree Program, Department of Pharmaceutical Sciences
School of Pharmacy & Pharmaceutical Sciences
School of Pharmacy & Pharmaceutical Sciences
Ph.D., University of California, Los Angeles, 1977, Neuroscience
University of California, Irvine
Department of Pharmaceutical Sciences
350A Med Surge II
Mail Code: 4625
Irvine, CA 92697
Department of Pharmaceutical Sciences
350A Med Surge II
Mail Code: 4625
Irvine, CA 92697
Research Interests
Estrogen, sex differences, cerebral vascular pharmacology, stroke, migraine
Academic Distinctions
2001, UCI Chancellor’s Award for Excellence in (Mentoring) Undergraduate Research
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.
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.
Awards and Honors
2009. American Heart Association Harold and Henrietta Lee Award
Short Biography
Diana N. Krause, Ph.D. is Adjunct Professor of Pharmaceutical Sciences at the University of California, Irvine, School of Pharmacy & Pharmaceutical Sciences. She is also a guest Professor of Pharmacology at University of Lund, Sweden. She received her Ph.D. in Neuroscience from UCLA and has a strong background in neuropharmacology. For over 25 years, Dr. Krause has been a pioneer in elucidating the influence of gender and sex steroid hormones on the cerebral vasculature. Her work has defined underlying mechanisms by which sex hormones, in particular estrogen, affect arterial contractility, endothelial function, vascular inflammation and mitochondrial function in physiological states and with pathophysiological insults such as stroke. Her current focus is to understand the basis for sex differences and hormonal influences on migraine headache, a debilitating disorder that disproportionally affects women.
Publications
Edvinsson, L. and Krause, D.N., Eds. Cerebral Blood Flow and Metabolism, 2nd Edition, Lippincott, Williams & Wilkins, Philadelphia, PA, 2002
Krause DN, Warfvinge K, Haanes K, Edvinsson L. Hormonal influences in migraine - interactions of oestrogen, oxytocin and CGRP. Nature Rev Neurol 17:621-633, 2021.
Edvinsson L, Haanes KA, Warfvinge K, Krause DN. CGRP as the target of new migraine therapies – a successful translation from bench to clinic. Nature Rev Neurol. 14:338-350, 2018
Warfvinge K, Krause DN, Maddahi A, Grell AS, Edvinsson JC, Haanes KA, Edvinsson L. Oxytocin as a regulatory neuropeptide in the trigeminovascular system: Localization, expression and function of oxytocin and oxytocin receptors. Cephalalgia 40:1283-1295, 2020
Warfvinge K, Krause D, Edvinsson L. The distribution of oxytocin and the oxytocin receptor in rat brain: relation to regions active in migraine. J Headache Pain 21:10, 2020
Warfvinge K, Krause DN, Maddahi A, Edvinsson JCA, Edvinsson L, Haanes KA. Estrogen receptors a, ß and GPER in the CNS and trigeminal system – molecular and functional aspects. J Headache Pain 21:131, 2020.
Edvinsson JCA, Warfvinge K, Krause DN, Blixt FW, Sheykhzade M, Edvinsson L, Haanes KA. C-fibers may modulate adjacent Ad-fibers through axon-axon CGRP signaling at nodes of Ranvier in the trigeminal system. J Headache Pain 20:105-115, 2019
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
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.
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
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
Doolen S, Krause DN, Dubocovich ML and Duckles SP. Melatonin mediates two distinct responses in vascular smooth muscle. Eur J Pharmacol 345:67-69, 1998
Krause DN and Dubocovich ML. Melatonin Receptors. Ann. Rev. Pharmacol. Toxicol. 31:549-568, 1991
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
University of Lund, Sweden 2011—pres
Graduate Programs
Pharmacological Sciences
Link to this profile
https://faculty.uci.edu/profile/?facultyId=2231
https://faculty.uci.edu/profile/?facultyId=2231
Last updated
01/06/2023
01/06/2023