Headerimage B. Vascular remodelling

B. Vascular remodelling

Vascular Remodelling and Reverse-remodelling

Research Area Leaders

Prof. Dr. Dr. Friedrich Grimminger

  • Dept. of Internal Medicine,
  • Medical Clinic V
    Klinikstrasse 33
    35392 Giessen
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Prof. Dr. Ralph T. Schermuly

Prof. Dr. Ralph T. Schermuly

  • Universities of Giessen & Marburg Lung Center
    Aulweg 130
    35392 Giessen
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Faculty involved

S. Bellusci, T. Braun, S. Dimmeler, B. Fisslthaler, I. Fleming, H.A. Ghofrani, F. Grimminger, J. Lohmeyer, E. Mayer, S. Offermanns, M. Potente, S.S. Pullamsetti, R.T. Schermuly, L. Schmitz, D. Schranz, W. Seeger, N. Weissmann, A.M. Zeiher

 

Subject

This Area focuses on maladaptive vascular and cardiac remodelling processes. Inward vascular remodelling is the hallmark of pulmonary hypertension (PH), and is found in atherosclerosis, systemic hypertension and post-injury restenosis. Restoration of physiological vascular structure and function (reverse remodelling) represents the therapeutic goal. Based on seminal basic findings, the establishment of large biobanks/registries and major translational achievements in the last funding period, the following topics will be addressed:

  1. receptor tyrosine kinase (RTK) enzymes engaged in growth factor signalling in PH will be profiled, selective intervention strategies will be developed and RTK inhibitor therapy will be refined in preclinical and clinical trials;
  2. transcription factors implicated in (reverse) remodelling will be studied, focusing on the FoxO, Wnt/ -catenin and Notch signalling pathways;
  3. exploitation of the NO-soluble guanylyl cyclase– cGMP–phosphodiesterase axis for the treatment of PH will be further refined and the clinical trial programme expanded;
  4. microRNAs that are functionally relevant in atherosclerosis and PH will be identified and explored as targets for prevention and therapy;
  5. the role of G-protein-mediated signalling in the regulation of vascular smooth muscle tone and differentiation will be dissected to develop new anti-proliferative treatment strategies, and
  6. pro-angiogenic cells will be manipulated and employed for the induction of angiogenesis in obliterated vessels. Moreover, addressing hypertrophy and failure of the right ventricle (RV) in response to PH, we aim to
    1. identify chamber-specific regulatory circuits as targets for specific RV therapy,
    2. exploit cardiomyocyte dedifferentiation and BMP-9/10 signalling for  myocardial adaptation to increased afterload, and
    3. perform clinical trials addressing right heart-focused therapy in PH.