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Laboratory of molecular cardiovascular physiology


Brief introduction

Our research focuses on the regulatory mechanisms of the circulatory system, on the subcellular, cellular, tissue and organism levels. Our objective is to elucidate the molecular mechanisms of physiological processes and, at the same time, to unravel their functional disorders in certain pathological conditions (e.g. dyslipidemia, diabetes, cerebral trauma and stroke). In our investigations we apply both modern pharmacological and genetic engineering techniques, in order to build, through disclosing the normal and pathological pathways of regulatory processes, a theoretical basis for the development of novel therapies for disorders of the cardiovascular system.

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Staff

Group Leader: Dr. Zoltán Benyó, Professor of Physiology
Dr. Péter Sándor, emeritus professor
Dr. Béla Horváth, adjunct professor
Dr. Éva Ruisanchez, assistant professor
Dr. Bernadett Faragó, research associate
Dr. András Iring, PhD student
László Hricisák, biologist
Mrs. Éva Körmöci, technician
Mrs. Margit Nagy, technician
Péter Tibor Dancs, medical student
Bálint Dér, medical student
Dávid Ádám Korda, medical student
Dorottya Móré, medical student
Andreas Polycarpou, medical student
Safar Daniel, medical student
Zsuzsa Straky, medical student

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Research projects

Vascular regulatory mechanisms adequately supporting normal tissue perfusion under physiological conditions undergo complex changes in pathological states. The aim of our research is to understand physiological regulatory mechanisms at the molecular level and to elucidate their changes under pathophysiological conditions. Within this field, we study the following specific problems:

Role of lisophospholipid mediators in the regulation of the vascular tone:

In the past decade our knowledge of sphyngosine-1-phosphate (S1P) and lysophosphatidic acid (LPA), two representatives of biological mediators deriving from phospholipids has increased by leaps and bounds. Several receptors of these mediators are present in the endothelium and in vascular smooth muscle, and they appear to play important roles in the regulation of various vascular functions of physiological as well as medical importance (vascular tone, permeability, blood vessel formation, smooth muscle proliferation etc.). Of these, we mainly address the effects on vascular tone and the intracellular signal transduction processes mediating these effects.

Signal transduction mechanisms of thromboxane receptors in vascular smooth muscle:

Thromboxane A2 (TXA2) is one of the most potent vasoconstrictor mediators of the circulatory system and, more specifically, of the cerebral vascular system. The effects of TXA2 are mediated by G-protein-linked cell surface receptors. Since TXA2 is capable of eliciting very strong, tonic contractions in cerebral blood vessels, it may be assumed to play a role in the development of cerebral vasospasm after subarachnoid hemorrhage, ischemic stroke and cerebral trauma. Our objective is to identify the signal transduction processes mediating the effects of TXA2 under physiological conditions, and to determine how these mechanisms are modified in the above-mentioned pathological conditions.

The role of vascular factors in the development of late neuronal damage following cerebral trauma

It is a well-known phenomenon that after cerebral trauma, the number of necrotized neurons and, consequently, the neurological deficit caused may increase continuously for as long as weeks and months. The dysfunction of the cerebral vasculature and the consecutive cerebral ischemia play an important role in the development of this secondary lesion. We aim to identify the mediators involved in vascular dysfunction and the pathological signal transduction processes operating in the cells of the blood vessel wall.

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Research techniques

Classical and tissue-specific conditional gene deletion techniques

Tissue blood flow measurement by laser speckle and laser Doppler techniques

Studies on the responsiveness of isolated blood vessels

Human and mouse endothelial cell cultures

Determination of the intracellular Ca2+-level

Analysis of gene expression by immunohistochemistry, Western blots and in situ hybridisation

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Representative publications

  1. Ruisanchez É, Cselenyák A, Papp RS, Németh T, Káldi K, Sándor P, Benyó Z: Perivascular expression and potent vasoconstrictor effect of dynorphin A in cerebral arteries. PLoS ONE, 2012; 7: e37798 (IF: 4,411)
  2. Horváth B, Lenzsér G, Benyó B, Németh T, Benkő R, Iring A, Hermán P, Komjáti K, Lacza Z, Sándor P, Benyó Z: Hypersensitivity to thromboxane receptor mediated cerebral vasomotion and CBF oscillations during acute NO-deficiency in rats. PLoS ONE, 2010; 5: e14477 (IF: 4,411)
  3. Wirth A, Benyó Z, Lukasova M, Leutgeb B, Wettschureck N, Gorbey S, Őrsy P, Horváth B, Maser-Gluth C, Greiner E, Lemmer B, Schütz G, Gutkind S, Offermanns S. G12/G13-LARG-mediated signalling in vascular smooth muscle is required for salt-induced hypertension. Nature Medicine, 14: 64-68, 2008 (IF: 27,553)
  4. Hortobágyi L, Kis B, Hrabák A, Horváth B, Huszty G, Schweer H, Benyó B, Sándor P, Busija DW, Benyó Z. Adaptation of the hypothalamic blood flow to chronic nitric oxide deficiency is independent of vasodilator prostanoids. Brain Research, 1131: 129-137, 2007 (IF: 2,218)
  5. Benyó Z, Gille A, Bennett C, Clausen B, Offermanns S. Nicotinic acid-induced flushing is mediated by activation of epidermal Langerhans cells. Molecular Pharmacology, 70(6): 1844-1849, 2006 (IF: 4,469)
  6. Benyó Z, Gille A, Kero J, Csiky M, Suchánková MC, Nüsing RM, Moers A, Pfeffer K, Offermanns S. GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. Journal of Clinical Investigation, 115: 3634-3640, 2005 (IF: 15,053)
  7. Horváth B, Hrabák A, Káldi K, Sándor P, Benyó Z Contribution of the heme oxygenase pathway to the maintenance of the hypothalamic blood flow during diminished NO synthesis. Journal of Cerebral Blood Flow and Metabolism, 23: 653-657, 2003 (IF: 5,370)
  8. Lacza Z, Hermán P, Görlach C, Hortobágyi T, Sándor P, Wahl M, Benyó Z. NO synthase blockade induces chaotic cerebral vasomotion via activation of thromboxane receptors. Stroke, 32: 2609-2614, 2001 (IF: 5,330)
  9. Iring A, Ruisanchez É, Leszl-Ishiguro M, Horváth B, Benkő R, et al. (2013) Role of Endocannabinoids and Cannabinoid-1 Receptors in Cerebrocortical Blood Flow Regulation. PLoS ONE 8(1): e53390. (IF: 4,092)

 

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Research grants

2009–2012: Zoltán Benyó: “The role of G-proteins in the regulation of cerebral vascular function”
National Innovation Office of Hungary
150.000 EUR

2012–2014: Zoltán Benyó: “Signal transduction processes of thromboxane receptors in vascular smooth muscle”
Hungarian Scientific Research Fund
100.000 EUR

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Research cooperations

STEFAN OFFERMANNS and NINA WETTSCHURECK
Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany

GÁBOR TIGYI
Department of Physiology, University of Tennessee Health Science Center, Memphis, USA

DAVID W. BUSIJA
Department of Pharmacology, Tulane University, New Orleans, USA

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