Update

The Medical Faculty of Heidelberg University has awarded Dr. Larissa Pfisterer the Friedrich Reutner-Prize. The young scientists studies how chronically elevated blood pressure affects the blood vessels. She discovered that a drug used to treat cancer can inhibit the detrimental chain reaction.

Press release of the Medical Faculty of Heidelberg University (in German)

Professor Thomas Korff of the Department of Physiology and Pathophysiology at Heidelberg University, Germany, will be awarded the German Research Foundation (DFG)'s Ursula M. Händel Animal Welfare Prize on March 20, 2014, at a ceremony in Berlin. The physiologist investigates the formation and remodeling of blood vessels and has developed methods that minimize the distress experienced by animals and reduce the number of test animals. In certain areas, animal experiments can be replaced completely. Professor Korff plans to use the prize money in the amount of 100,000 euros to refine his methods and standardize them so that they can be introduced and applied in other research laboratories without a great deal of effort.

   
Blood vessels in the petri dish

The award winner and his group study the processes and mechanisms in blood vessels that underlie normal development as well as pathological remodeling processes associated with, e.g. atherosclerosis or varicose veins. In order to use human cells for his experiments to the greatest extent possible, Korff has developed special culture methods. To this end, he cultivates spherical cellular aggregates from cells that are isolated from the blood vessels of human umbilical cord after birth. These cell masses mimic two layers of the vessel wall.

This model system for human blood vessels is not only well suited for basic research, but is now also being used in industrial applications. Scientists from Beiersdorf AG in Hamburg, Germany, are using the model system to test the protective effect of cosmetic substances on microscopic skin vessels. "Since we categorically excludeanimal testing, we use these kinds of realistic methods with human cells, which are especially significant for us," said Dr. Gitta Neufang, Head of Medical Management at Beiersdorf AG.

  
Test mice affected as little as possible

  
"However, cell cultures reach their limits for applications beyond cosmetics, for instance, if we want to find out how and why vessels undergo pathological changes," Korff pointed out. In this case, it is not possible to avoid direct manipulations on animals, he clarified. ìHowever, we have developed new surgical techniques that are much less stressful for the test animal than other proceduresused in vascular research." The new methods are easy to perform and mean less distress for the animals. "The animals behave normally and the success rate of the surgical procedures is higher. We need fewer animals for reliable results, which also reduces the costs," he added.

For experiments on the living organism, the team often uses the ear of the mouse, in which the blood vessels are already clearly visible with the naked eye. The mouse ear is also easily accessible for many imaging techniquesand is suitable as a model for investigating many research questions. Without a single incision, for instance, a vein can be tied off in order to raise blood pressure in the afferent vessels. In so doing, the formation of varicose veins can be simulated and their development observed over a period of several days. With this model, Korff investigates what signal pathways and molecules promote the pathological enlargement of the veins and whether certain substances can influence it. These kinds of studies are essential for identifying approaches for future therapeutic treatment.

In another project, the research group uses the mouse ear to investigate how tumors influence existing vessels or stimulate the formation of new vessels and, in so doing, can ensure their own blood supply. "Processes that are so complex can only be studied in live animals," Korff explained.
 

Literature:

Demicheva E, Hecker M, Korff T. Stretch-induced activation of the transcription factor activator protein-1 controls monocyte chemoattractant protein-1 expression during arteriogenesis.

Circ Res. 2008 Aug 29;103(5):477-84.Feldner A, Otto H, Rewerk S, Hecker M, Korff T. Experimental hypertension triggers varicosis-like maladaptive venous remodeling through activator protein-1.

FASEB J. 2011 Oct;25(10):3613-21.Navid F, Kolbe L, Stäb F, Korff T, Neufang G. UV radiation induces the release of angiopoietin-2 from dermal microvascular endothelial cells. Exp Dermatol. 2012 Feb;21(2):147-53.

More information is available on the Web:

Working Group Prof. Dr. Thomas Korff:http://www.medizinische-fakultaet-hd.uni-heidelberg.de/Korff-Group.110926.0.html?&L=en

DFG Press release: http://www.dfg.de/en/service/press/press_releases/2014/press_release_no_04/index.html

Ursula M. Händel Animal Welfare Prize:www.dfg.de/haendel-prize

Dr. Larissa Pfisterer, Division of Cardiovascular Physiology at the Institute of Physiology and Pathophysiology , Heidelberg University, received the dissertation award at the Scientific Congress of the German Hypertension League (DHL) in Münster on 12 December. In her work she identified a new signaling pathway that controls the pathological changes of arteries in hypertension. Key molecule is myocardin, which regulates the expression of proteins that allow vascular smooth muscle cells to respond to normal changes in blood pressure by contraction. In chronic hypertension the protein is modified so that it loses its function and is degraded. In the cells this initiates processes that may lead to a thickening of the vessel wall and in consequence to a dangerous vasoconstriction. The signaling pathway could thus offer an interesting target for new therapeutic approaches.

The annual award, which comes with a prize money of 3,000 euro, was shared this year. Second prize winner is Dr. Pia Jeggle, who received her doctorate at the University of Münster.

Pfisterer L, Feldner A, Hecker, M, Korff T. Hypertension impairs myocardin function - a novel mechanism facilitating arterial remodeling. Cardiovasc Res. 2012 Oct 1;96(1):120-9.

At the 37th Congress of the International Union of Physiological Sciences held at the end of July in Birmingham, UK, Prof. Markus Hecker, Director of the Institute of Physiology and Pathophysiology, Heidelberg University, Germany, was elected new president of the Federation of European Physiological Societies (FEPS). He will first join the seven-member FEPS Executive Committee as President-Elect for two years before serving a four-year term as President. His work on the board will end after another two years as Past-President.

 
FEPS comprises 30 national and transregional societies with well over 7500 members from more than 34 countries. It aims to promote the dissemination of novel physiological knowledge between basic scientists and physicians and the education in the field of physiology, among others, by facilitating the organization of annual international physiological congresses.

In the current edition of Science published on 21.12.2012 the scientific journal features the article by first authors Sahana Suresh Babu and Agnieszka Wójtowicz of the group of Privatdozent Marco Cattaruzza, Division of Cardiovascular Physiology, that appeared in Science Signaling 5(254) (see below) as Editors' Choice in the field of cell biology. In this section the renowned journal presents "highlights of the recent literature".

Editors' Choice: Cell Biology - Feeling the Stretch. Science 2012;338(6114):1513.

Acces to this page may require a valid subscription to the journal Science.

The December 11 online issue of “Science Signaling” features an image from an article by first authors Sahana Suresh Babu and Agnieszka Wójtowicz, former PhD students in the group of Privatdozent Marco Cattaruzza, Division of Cardiovascular Physiology, on its cover. The work, which was carried out in collaboration with researchers from the Institute of Pharmacology, Heidelberg University, and the Laboratory of Neurobiology, National Institute of Environmental Health Sciences, USA, describes the signaling pathway that activates the mechanotransducer protein zyxin in response to stretch in vascular cells.

Suresh Babu S, Wojtowicz A, Freichel M, Birnbaumer L, Hecker M, Cattaruzza M. Mechanism of stretch-induced activation of the mechanotransducer zyxin in vascular cells. Sci Signal. 2012 Dec 11;5(254):ra91 doi: 10.1126/scisignal.2003173

To directly access the article please follow the links under Publications.

Anja Feldner and Hannes Schroeder of the Institute of Physiology and Pathophysiology (Division of Cardiovascular Physiology), Heidelberg University, were awarded the UCB Pharma Prize at the annual meeting of the German Society of Angiology - Society for Vascular Medicine (DGA) on 12 September in Mainz. They were honored for their study on the molecular pathways involved in the development of varicose veins, which they had published as joint first authors in last year's October issue of the FASEB Journal. Their work showed that this venous disease is controlled by the transcription factor AP-1. This protein regulates the activity of genes whose products contribute to the changes in the vascular cells and the surrounding connective tissue, leading to the formation of the characteristic corkscrew veins. Using a specific animal model developed by the two biologists during their doctoral research in the laboratory of PD Dr. Thomas Korff, they could inhibit the activity of AP-1 and, as a result, the formation of varicose veins. These findings could lead to new drugs to prevent the development of varicose veins

The UCB Pharma prize, which is worth 10 000 euros and which is awarded annually by the DGA, was shared this year. In addition to the Heidelberg winners, Dr. Nora Gatzke and Dr. Philip Hill Master of the Berlin Charité were co-recipients of the award.

The Deutsche Gesellschaft für Angiologie-Gesellchaft für Gefäßmedizin e.V. (DGA, German Society of Angiology - Society for Vascular Medicine) is a multidisciplinary medical society for the promotion of research and training in the field of vascular medicine. In collaboration with other professional societies, associations and authorities, DGA physicians aim at preventing and fighting vascular disease. The DGA informs patients and people at risk about prevention, diagnosis and treatment. With its research awards the DGA specifically promotes young scientists.

Varicose veins, sometimes referred to as “varices” in medical jargon, are usually just a cosmetic problem if they occur as spider veins. In their advanced stage, however, they pose a real health threat. In people with this widespread disorder, the blood is no longer transported to the heart unhindered but instead pools in the veins of the leg. This is because the vessel walls or venous valves no longer function adequately. Dr. Thomas Korff and his group at the Division of Cardiovascular Physiology (Director: Prof. Markus Hecker) of Heidelberg University’s Institute of Physiology and Pathophysiology have now shown that the pathological remodeling processes causing varicose veins are mediated by a single protein. As a response to increased stretching of the vessel wall, this protein triggers the production of several molecules promoting changes in wall architecture. The paper published in the current issue of FASEB Journal may offer a possibility for using drugs to decelerate the formation of or even prevent new varicose veins.

Previously, no suitable experimental systems existed for studying the way in which these changes in the cells of the blood vessels are controlled. For their studies, Korff and his team took advantage of the fact that blood vessels in the mouse ear are clearly visible and are also easily accessible for minor surgical procedures. In order to artificially set off processes that are similar to the formation of varicose veins, they tied off a vein with a thin thread. The elevated pressure in the vessels caused by the pooled blood led to the recognizable remodeling characteristic of varicose veins. In addition, in the affected veins, the cell proliferation rate and the production of MMP-2 increased. MMP-2 is an enzyme that breaks down the non-cellular components of the connective tissue of the blood vessels. On the other hand, there were no signs of an inflammatory response, which can be observed during other vessel remodeling processes.

   
Model allows agents to be tested

“Nevertheless, the cellular mechanisms that control the formation of varicose veins appear to be similar to mechanisms that orchestrate the remodeling of arteries in patients with high blood pressure,” Korff explains. The transcription factor AP-1 which regulates the activity of certain genes and thus the corresponding protein production is regulated by the filling pressure in the blood vessels and in turn controls the formation of varicose veins, Korff adds. If AP-1 is inhibited, thus prohibiting it from activating genes, the characteristic corkscrew-like varicose veins do not form and cell proliferation and the production of enzymes that break down connective tissue remain at normal levels.

In a further experiment, the group showed that the results obtained in the mouse are also valid for humans. Varicose veins that have been surgically removed from patients exhibited the same cellular and molecular changes as the varicose veins created artificially in the mouse ear. Based on these results, Korff plans more studies. “Using our model, we can now more precisely analyze the early stages of the disorder and test possible drugs for their ability to prevent varicose vein formation, which, as a result, may improve the quality of life of afflicted patients.” According to the German Vascular League, 30 million people suffer from minor vein-related symptoms, whereby women are affected around twice as often as men.According to a health report published by the German government, 15 to 20 percent of the population has varicose veins.

Feldner A, Otto H, Rewerk S, Hecker M, Korff T. Experimental hypertension triggers varicosis-like maladaptive venous remodeling through activator protein-1. FASEB J. 2011 Oct;25(10):3613-21. Epub 2011 Jun 17.

The article Experimental hypertension triggers varicosis-like maladaptive venous remodeling through activator protein-1 by the Working Group Korff, Division of Cardiovascular Physiology, is featured on the cover of the October issue of the FASEB Journal.