Header Bild Mueller Dechend

Müller/Dechend Lab

Hypertension-caused End-Organ Damage

Profile

In a translational approach, combining animal models, in vitro studies and human cohorts, we focus on the crosstalk between immune cells, vasculature and target organs of hypertension.

The group’s major research interests are the renin-angiotensin system,the immune systemand how both systems cause hypertension-induced target-organ damage.

Recent work has extended the concept analyzing how environmental factors such as a high salt affect the microbiome, immune cells, target organs, and autoimmunity. In a translational approach, the Dechend/Müller laboratory focuses primarily on the placenta, heart, and kidneys.

The group also cooperates closely with MDC scientists and Charité clinician scientists and has also been a resource for young clinicians and doctoral students beginning their careers in experimental and clinical cardiovascular research.

Team

Research

 

Preeclampsia

 

Preeclampsia is an acute emergent hypertensive “target-organ” condition of pregnancy, characterized by hypertension and proteinuria. It affects 3-10% of all pregnancies worldwide. Preeclampsia is a major health problem, responsible for approximately 50 000 maternal deaths annually. Women who develop preeclampsia and children of preeclamptic pregnancies are at increased risk of coronary heart disease, stroke and cardiovascular disease in later life. The cause of preeclampsia is unknown.

Our research program on this disease involves patient-oriented and basic research studies, including animal models. Our primary focus has been on understanding Cytochrome P450-related mechanisms, angiogenesis and auto-antibodies (renin-angiotensin system). Agonistic auto-antibodies to the angiotensin II receptor type I (AT1-AA) have been identified in preeclamptic mothers and fetus, and induce signal transduction including protein kinase C and the mitogen-activated protein pathway, resulting in the activation of transcription factors NF-kB and AP-1. We have identified AT1-AA in various rat models of preeclampsia. Subsequently we have provided experimental in vivo evidence that AT1-AA account for the observed reduction in Ang II sensitivity observed in preeclamptic patients. We are also investigating new therapeutic targets in a transgenic rat model that features key characteristics of preeclampsia. With this rat model we have established state of the art diagnostic procedures, routinely performed in the clinic for pregnant women, enabling us to show a causal link between reduced trophoblast invasion and placental perfusion. In clinical studies, we are currently investigating physiological parameters and identifying novel biomarkers during and after preeclampsia, which may help to explain the increased cardiovascular risk of former preeclamptic patients. Besides AT1 receptor antibodies, we are also investigating the role of ANP, GDF-15, sFlt1 and CRP. Präeklampsie, Berlin

Recently published

Kvehaugen AS, Melien O, Holmen OL, Laivuori H, Oian P, Andersgaard AB, Dechend R, Staff AC.
Single Nucleotide Polymorphisms in G Protein Signaling Pathway Genes in Preeclampsia.
Hypertension. 2013 Jan 21.
PMID: 23339167

Herse F, Lamarca B, Hubel CA, Kaartokallio T, Lokki AI, Ekholm E, Laivuori H, Gauster M, Huppertz B, Sugulle M, Ryan MJ, Novotny S, Brewer J, Park JK, Kacik M, Hoyer J, Verlohren S, Wallukat G, Rothe M, Luft FC, Muller DN, Schunck WH, Staff AC, Dechend R.

CYP2J2 Expression and Circulating Epoxyeicosatrienoic Metabolites in Preeclampsia.
Circulation. 2012 Dec 18;126(25):2990-9.
PMID: 23155181

Novotny SR, Wallace K, Heath J, Moseley J, Dhillon P, Weimer A, Wallukat G,Herse F,Wenzel K, Martin JN Jr, Dechend R, Lamarca B.
Activating autoantibodies to the angiotensin II type I receptor play an important role in mediating hypertension in response to adoptive transfer of CD4+ T lymphocytes from placental ischemic rats.
Am J Physiol Regul Integr Comp Physiol. 2012 May 15;302(10):R1197-201. Epub 2012 Mar 28.
PMID: 22461177

Dhillion P, Wallace K, Herse F, Scott J, Wallukat G, Heath J, Mosely J, Martin JN Jr, Dechend R, Lamarca B.
IL-17-mediated oxidative stress is an important stimulator of AT1-AA and hypertension during pregnancy.

Am J Physiol Regul Integr Comp Physiol. 2012 Aug;303(4):R353-8. Epub 2012 Jun 20.
PMID: 22718806

Jensen F, Wallukat G,Herse F, Budner O, El-Mousleh T, Costa SD, Dechend R, Zenclussen AC.

CD19+CD5+ Cells as Indicators of Preeclampsia.

Hypertension. 2012 Feb 21.

PMID: 22353610

Herse F*, Sugulle M,Hering L, Mockel M,Dechend R, Staff AC.

Cardiovascular biomarker midregional proatrial natriuretic Peptide during and after preeclamptic pregnancies.

Hypertension. 2012 Feb;59(2):395-401. Epub 2011 Dec 19.

PMID: 22184318

Searle J, Mockel M, Gwosc S, Datwyler SA,Qadri F, Albert GI, Holert F, Isbruch A, Klug L,Muller DN, Dechend R, Muller R, Vollert JO, Slagman A, Mueller C, Herse F.

Heparin strongly induces soluble fms-like tyrosine kinase 1 release in vivo and in vitro--brief report.

Arterioscler Thromb Vasc Biol. 2011 Dec;31(12):2972-4. Epub 2011 Oct 6.

PMID: 21979436

Kvehaugen AS, Dechend R, Ramstad HB, Troisi R, Fugelseth D, Staff AC.

Endothelial function and circulating biomarkers are disturbed in women and children after preeclampsia

Hypertension. 2011 Jul;58(1):63-9.

PMID: 21606387

Recently reviewed

Herse F, Lamarca B.

Angiotensin II Type 1 Receptor Autoantibody (AT1-AA)-Mediated Pregnancy Hypertension.

Am J Reprod Immunol. 2012 Dec 28.

PMID: 23279165

Staff AC,Dechend R, Redman CW.

Review: Preeclampsia, acute atherosis of the spiral arteries and future cardiovascular disease: Two new hypotheses.

Placenta. 2012 Dec 13.

PMID: 23246096

Dechend R, Staff AC

Placenta messages to the mother: not just debris.

Hypertension. 2012 Feb;59(2):191-3.

PMID: 22215710

Verlohren S, Stepan H, Dechend R.

Angiogenic growth factors in the diagnosis and prediction of pre-eclampsia.

Clin Sci (Lond). 2012 Jan;122(2):43-52.

PMID: 21929511

All publications

pudmed

Immune-Salt-Mircrobiome

The immune system, salt and hypertension-induced target organ damage

Hypertension induces target-organ damage; however, the mechanisms are unclear. In general, the immune system is traditionally considered to be a complex biological system that wards off disease, typically by fighting the invasion of foreign microorganisms, such as bacteria and viruses. We and others found that the immune system plays a pivotal role in the pathogenesis of Angiotensin (Ang) II-induce target-organ damage. 
Together with Jens Titze (Vanderbilt University), we address the regulatory interaction between immune cells, lymph vessels, and interstitial matrix components for maintenance of internal environmental composition, blood-pressure regulation, cardiovascular target-organ damage, and immunity. We provided evidence that sodium, a known risk factor for cardiovascular disease, interacts with the immune system. Increased NaCl concentrations induced an increase in the cytokine-driven TH17 activation in naïve T cells and alter M1 and M2 macrophage action. The outcome of this increased TH17 activation resulted in an accelerated and more severe autoimmune disease (multiple sclerosis) in mice on a high-salt diet.
Macrophages are an important innate immune cell type, which fulfills a plethora of homeostatic functions beyond host defense. Functional diversity is reflected by a continuous spectrum of different activation states and M(LPS) also referred to as “M1” and M(IL-4+IL-13) also referred to as “M2” may be viewed as the extreme pro- and anti-inflammatory poles of macrophage activation, respectively. Similar to T cells, physiologically increased environmental sodium concentrations affected pro- and anti-inflammatory activation of macrophages differentially. Pro-inflammatory activation of macrophages with LPS was significantly boosted in the presence of high NaCl concentrations and enhanced inflammatory mediator and effector molecule expression.
In contrast, for murine M2 macrophages activated with IL-4+IL-13 recently found that activation was blunted in vitro and in vivo.1 For instance, M(IL-4+IL-13) cells activated in the presence of additional NaCl had a significantly reduced ability to suppress CD4+ T cell proliferation in vitro and a high-salt diet delayed cutaneous wound healing. Salt effect on M(IL-4+IL-13) activation was independent of tonicity. Instead, we found evidence that salt affected M2 macrophages via an Akt-mTOR metabolic signaling pathway and changes in cellular metabolism. It is now acknowledged that adaptions of cellular metabolic programs are crucial for proper immune cell activation. Metabolic “rewiring” is not simply adopted to meet the energetic needs of blasting lymphocytes; instead, it also controls effector functions and fate decisions of adaptive immune cells. One future research goal of our laboratory is to elucidate the role of salt on immunometabolism and immune cell function.

Clinical Studies

Translational approach combining animal models, in vitro models and human cohort studies

Our group research interests will be investigated in a translational approach, combining animal models, in vitro models and human cohort studies. These clinical studies are very important to connect and proof the basic research in a clinical approach.

Our clinical studies will be done in the rooms of the Clinical Research Center at the ECRC and in cooperation with our clinical partners, HELIOS Klinikum Berlin-Buch, Charité Campus Mitte, Charité Campus Virchow and the Vivantes Klinikum Neukölln, and international collaborators.

Following studies are currently under investigation:

Study title

Proband information

Clinical trials

Untersuchung zur Immunophänotypisierung im Zusammenhang mit Bluthochdruck- und Diabeteserkrankungen.

Interner link

 

Untersuchung zur Immunzell-Tophoblasten-Interaktion im Zusammenhang mit Schwangerschaftserkrankungen

(Berlin-Brandenburg-Pregnancy Cohort (BBPC))

Interner link

NCT03313024

Untersuchung des Myokards mittels Kardio-MRT an Patientinnen nach Präeklampsie (Pilot-Studie) (Post-Pregnancy Cohort 1)

Interner link

NCT03313063

Previous Studies:

Study title

contact

Agonistic angiotensin II type 1 receptor autoantibodies in postpartum women with a history of preeclampsia.

Dr. Florian Herse, Dr. Ralf Dechend

Dysregulation of the circulating and tissue-based renin-angiotensin system in preeclampsia.

Dr. Florian Herse, Dr. Ralf Dechend

Potential relevance of alpha(1)-adrenergic receptor autoantibodies in refractory hypertension.

Dr. Ralf Dechend

Prevalence of agonistic autoantibodies against the angiotensin II type 1 receptor and soluble fms-like tyrosine kinase 1 in a gestational age-matched case study.

Dr. Florian Herse, Dr. Ralf Dechend

Circulating and uteroplacental adipocytokine concentrations in preeclampsia.

Dr. Florian Herse, Dr. Ralf Dechend

A recently evolved novel trophoblast-enriched secreted form of fms-like tyrosine kinase-1 variant is up-regulated in hypoxia and preeclampsia.

Dr. Florian Herse, Dr. Ralf Dechend

Circulating and placental growth-differentiation factor 15 in preeclampsia and in pregnancy complicated by diabetes mellitus.

Dr. Florian Herse, Dr. Ralf Dechend

Adipose tissue-derived soluble fms-like tyrosine kinase 1 is an obesity-relevant endogenous paracrine adipokine

Dr. Florian Herse, Dr. Ralf Dechend

Heparin strongly induces soluble fms-like tyrosine kinase 1 release in vivo and in vitro

Dr. Florian Herse, Dr. Ralf Dechend

Cardiovascular biomarker midregional proatrial natriuretic peptide during and after preeclamptic pregnancies.

Dr. Florian Herse, Dr. Ralf Dechend

Cardiovascular risk markers in pregnancies complicated by diabetes mellitus or preeclampsia.

Dr. Florian Herse, Dr. Ralf Dechend

Cytochrome P450 subfamily 2J polypeptide 2 expression and circulating epoxyeicosatrienoic metabolites in preeclampsia.

Dr. Florian Herse, Dr. Ralf Dechend

Interfering with Gal-1-mediated angiogenesis contributes to the pathogenesis of preeclampsia.

Dr. Florian Herse, Dr. Ralf Dechend

Placental miR-1301 is dysregulated in early-onset preeclampsia and inversely correlated with maternal circulating leptin.

Dr. Florian Herse, Dr. Ralf Dechend

Increased Apoptosis, Altered Oxygen Signaling, and Antioxidant Defenses in First-Trimester Pregnancies with High-Resistance Uterine Artery Blood Flow.

Dr. Florian Herse, Dr. Ralf Dechend

 

Funding

 

 

Project Title, Type of grant

Funding Agency

Vitamin D in preeclampsia

DFG

Novel diagnostics tool in preeclampsia

The Federal Ministry for Economic Affairs and Energy

Novel  ELISAs against soluble Stabilin-1 and Stablilin-2

The Federal Ministry for Economic Affairs and Energy

Fetal programing in pregnancy

BIH (Berlin Institute of Health)

Epigenetic disturbances in preeclampsia

BIH (Berlin Institute of Health)

In vitro diagnostics

The Federal Ministry for Economic Affairs and Energy

NF-kB in AKI

DFG

Microbiome

DZHK German Center for Cardiovascular Research

Cardiovascular endorgan damage after preeclampsia

BIH (Berlin Institute of Health)

Influence of angiotensin II on placental fractalkin

DFG

               

Mechanisms of immune-tolerance in pregnancy

DFG

CD74 in macrophage-trophoblastic interactions in preeclampsia

DFG

CYP2J2 and it’s metabolites in preeclampsia

DFG

Autoantibodies and anti-angiogenic factors from patients with preeclampsia

The Federal Ministry for Economic Affairs and Energy

 

 

 

Publications

Studien

Die Forschungsgruppe Müller/Dechend am Experimental & Clinical Research Center (ECRC) des Max-Delbrück-Centrums für Molekulare Medizin und der Charité Campus Buch führt verschiedene klinische Studien durch, für die Teilnehmer gesucht werden.

Untersuchung zur Immunzell-Tophoblasten-Interaktion im Zusammenhang mit Schwangerschaftserkrankungen (Berlin-Brandenburg-Pregnancy Cohort)

 

Sehr geehrte Schwangere,

die Forschungsgruppe Müller/Dechend am Experimental & Clinical Research Center (ECRC) des Max-Delbrück-Centrum für Molekulare Medizin und der Charité Campus Buch untersucht die Entstehung und die Folgen von Bluthochdruckerkrankungen. Ein Forschungsgebiet davon bildet die Schwangerschaftserkrankung Präeklampsie. Bei dieser Erkrankung kommt es während der Schwangerschaft zu einem plötzlichen Anstieg des Blutdruckes einhergehend mit einer Eiweißausscheidung in den Urin.

Zur Erforschung von Faktoren und deren Einfluss auf die Erkrankung möchten wir Zellen, Zellfragmente und weitere Bestandteile des Blutes analysieren. Des Weiteren sollen Erkenntnisse aus einem allgemeinen Gesundheits-Check gewonnen werden. Hierdurch versprechen wir uns wichtige Einblicke in die Entstehung der Präeklampsie und den generellen Verlauf einer Schwangerschaft zu erlangen.

Wir würden Sie gerne zur Teilnahme an einer Studie einladen. Diese sieht eine Blutentnahme und einen allgemeinen Gesundheits-Check zu 3 verschiedenen Zeitpunkten während der Schwangerschaft vor.

Studienablauf

 

Teilnehmen können alle schwangeren Frauen im Alter zwischen 18 und 45 Jahren. Für die Teilnahme wird eine angemessene Aufwandsentschädigung gezahlt.

Haben wir Ihr Interesse geweckt?

Dann melden Sie sich bitte telefonisch oder per E-Mail bei uns.

Kontakt: Heike Schenck

Telefon 030 450 540 565

E-Mail: ecrc-schwangerschaftsstudie@charite.de

            Stichwort: Schwanger

Untersuchung des Myokards mittels Kardio-MRT an Patientinnen nach Präeklampsie (Pilot-Studie) (Post-Pregnancy Cohort 1)

 

Die Forschungsgruppe Müller/Dechend am Experimental & Clinical Research Center (ECRC) des Max-Delbrück-Centrum für Molekulare Medizin und der Charité Campus Buch untersucht die Entstehung und die Folgen von Bluthochdruck. Ein Forschungsgebiet davon bildet die Schwangerschaftserkrankung Präeklampsie. Bei dieser Erkrankung kommt es während der Schwangerschaft zu einem plötzlichen Anstieg des Blutdruckes einhergehend mit einer Eiweißausscheidung in den Urin. Nach einer präeklamptischen Schwangerschaft haben Mutter und Kind im späteren Leben ein erhöhtes Risiko für Herz-Kreislauf-Erkrankungen. Ursachen hierfür sind noch nicht vollständig untersucht und die krankhaften Veränderungen des Herzens bei Frauen nach präeklamptischer Schwangerschaft nicht grundlegend charakterisiert.

Wir möchten Sie gerne einladen, unser Forschungsprojekt zu unterstützen und an dieser Studie teilzunehmen.

Ziel unserer Studie ist die kardiologische Charakterisierung, insbesondere des Herzmuskels (Myokards), von Frauen nach präeklamptischer und Frauen mit normal verlaufender Schwangerschaft. Hierzu werden einige funktionelle Tests (kardiologischer Gesundheits-Check), eine Magnetresonanztomographie (MRT)-Untersuchung sowie eine Echokardiographie durchgeführt. Insgesamt sieht unsere Studie zwei Termine in Berlin-Buch und einen am Charité-Campus Virchow in Berlin-Wedding vor.

Studienablauf

Teilnehmen können Frauen die mit der Diagnose Präeklampsie oder einer normal verlaufenden Schwangerschaft in den letzten 20 Jahren ein Kind zur Welt gebracht haben und im Alter zwischen 18 und 50 Jahren sind. Für die Teilnahme wird eine angemessene Aufwandsentschädigung gezahlt.

Kontakt

 

 

Untersuchung zur Immunophänotypisierung im Zusammenhang mit Bluthochdruck- und Diabeteserkrankungen

 

Freiwillige Blutspender gesucht!

Projektleiter: Prof. Dr. Dominik Müller,   Tel.: (030) 450-540 286

Ansprechpartner: Dr. Andras Balogh,   Tel.: (030) 450-540 558

Wir suchen für eine Studie gesunde Männer und Frauen zwischen 18 und 70 Jahren die bereit sind sich unter ärztlicher Kontrolle 90 ml Blut entnehmen zu lassen. Aus dem Blut sollen Immunzellen isoliert und charakterisiert werden und in verschiedenen Zellkulturtests eingesetzt werden. Es wird eine angemessene Aufwandsentschädigung angeboten.

Bei Interesse wird den Probanden ein Einblick in die Analyseverfahren und die Forschung im Allgemeinen sehr gerne gewährt.

Sollten wir Ihr Interesse geweckt haben melden Sie sich bitte bei:

Dr. Andras Balogh

Tel.: (030) 450-540 558

Email: Andras.Balogh@mdc-berlin.de

 

Dominik Müller
Prof. Dr. Dominik Müller
PD Dr. Ralf Dechend
Group Leaders
Contacts
 
Prof. Dr. Dominik Müller
(030) 450 540286
42-52: Experimental and Clinical Research Center
Room 2634

 

 

PD Dr. Ralf Dechend
(030) 450 540301
42-52: Experimental and Clinical Research Center
Room 2625

 

Max-Delbrück-Centrum für Molekulare Medizin (MDC)
Robert-Rössle-Str. 10
13092 Berlin, Germany

 

Research Topics