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Group Vettel: Cardiac Remodeling

We are interested in signaling pathways involved the structural and arrhythmogenic remodeling that characterize the diseased heart. Our goal is to identify novel therapeutic targets for the treatment of heart failure patients.

Many of the relevant cardiac remodeling processes that precede heart failure are triggered by a chronic over-activation of the sympathetic nervous system (SNS) and persistently high levels of the pro-fibrotic hormone angiotensin II. The hormones released by the SNS exert their effects on cardiomyocytes through both α-and β-adrenergic receptors (α-and β-ARs).

We recently discovered a novel α-AR pathway involving the RacGEF Tiam1 that contributes to cardiac hypertrophy (Vettel et al., 2012), and demonstrated the protective effect of genetically reinforcing endogenous β-adrenergic desensitization mechanisms on cardiac performance after myocardial infarction and on arrhythmia susceptibility (Vettel et al., 2017). The models we use include primary cell culture systems e.g. isolated cardiomyocyte/cardiac fibroblasts from mouse or rat heart tissue, signal transduction analysis via pharmacological and genetic approaches, and vivo animal studies.

Neonatal rat cardiac fibroblasts
Neonatal rat cardiomyocyte
Cross section of a mouse heart

Recent Publications

  1. Dewenter M, Neef S, Vettel C, Lämmle S, Beushausen C, Zelarayan LC, Katz S, von der Lieth A, Meyer-Roxlau S, Weber S, Wieland T, Sossalla S, Backs J, Brown JH, Maier LS, El-Armouche A. Calcium/Calmodulin-Dependent Protein Kinase II Activity Persists During Chronic β-Adrenoceptor Blockade in Experimental and Human Heart Failure. Circ Heart Fail. 2017 May;10(5).
  2. Abu-Taha IH, Heijman J, Hippe HJ, Wolf NM, El-Armouche A, Nikolaev VO, Schäfer M, Würtz CM, Neef S, Voigt N, Baczkó I, Varró A, Müller M, Meder B, Katus HA, Spiger K, Vettel C, Lehmann LH, Backs J, Skolnik EY, Lutz S, Dobrev D, Wieland T. Nucleoside Diphosphate Kinase-C Suppresses cAMP Formation in Human Heart Failure. Circulation 2017 Feb 28;135(9):881-897.
  3. Vettel C, Lindner M, Dewenter M, Lorenz K, Schanbacher C, Riedel M, Lämmle S, Meinecke S, Mason FE, Sossalla S, Geerts A, Hoffmann M, Wunder F, Brunner FJ, Wieland T, Mehel H, Karam S, Lechêne P, Leroy J, Vandecasteele G, Wagner M, Fischmeister R, El-Armouche A. Phosphodiesterase 2 Protects Against Catecholamine-Induced Arrhythmia and Preserves Contractile Function After Myocardial Infarction. Circ Res. 2017 Jan 6;120(1):120-132.
  4. Swain L, Kesemeyer A, Meyer-Roxlau S, Vettel C, Zieseniss A, Güntsch A, Jatho A, Becker A, Nanadikar MS, Morgan B, Dennerlein S, Shah AM, El-Armouche A, Nikolaev VO, Katschinski DM. Redox Imaging Using Cardiac Myocyte-Specific Transgenic Biosensor Mice. Circ Res. 2016 Oct 14;119(9):1004-1016.
  5. Ongherth A, Pasch S, Wuertz CM, Nowak K, Kittana N, Weis CA, Jatho A, Vettel C, Tiburcy M, Toischer K, Hasenfuss G, Zimmermann WH, Wieland T, Lutz S. p63RhoGEF regulates auto- and paracrine signaling in cardiac fibroblasts. J Mol Cell Cardiol. 2015 Nov;88:39-54.
  6. Vettel C, Lämmle S, Ewens S, Cervirgen C, Emons J, Ongherth A, Dewenter M, Lindner D, Westermann D, Nikolaev VO, Lutz S, Zimmermann WH, El-Armouche A. PDE2-mediated cAMP hydrolysis accelerates cardiac fibroblast to myofibroblast conversion and is antagonized by exogenous activation of cGMP signaling pathways. Am J Physiol Heart Circ Physiol. 2014 Apr 15;306(8):
  7. Vettel C, Hottenrott MC, Spindler R, Benck U, Schnuelle P, Tsagogiorgas C, Krämer BK, Hoeger S, El-Armouche A, Wieland T, Yard BA. Dopamine and lipophilic derivates protect cardiomyocytes against cold preservation injury. J Pharmacol Exp Ther. 2014 Jan;348(1):77-85.
  8. Mehel H, Emons J, Vettel C, Wittköpper K, Seppelt D, Dewenter M, Lutz S, Sossalla S, Maier LS, Lechêne P, Leroy J, Lefebvre F, Varin A, Eschenhagen T, Nattel S, Dobrev D, Zimmermann WH, Nikolaev VO, Vandecasteele G, Fischmeister R, El-Armouche A. Phosphodiesterase-2 is up-regulated in human failing hearts and blunts β-adrenergic responses in cardiomyocytes. J Am Coll Cardiol. 2013 Oct 22;62(17):1596-606.
  9. Felcht M, Luck R, Schering A, Seidel P, Srivastava K, Hu J, Bartol A, Kienast Y, Vettel C, Loos EK, Kutschera S, Bartels S, Appak S, Besemfelder E, Terhardt D, Chavakis E, Wieland T, Klein C, Thomas M, Uemura A, Goerdt S, Augustin HG. Angiopoietin-2 differentially regulates angiogenesis through TIE2 and integrin signaling. J Clin Invest. 2012 Jun;122(6):1991-2005.
  10. Vettel C, Wittig K, Vogt A, Wuertz CM, El-Armouche A, Lutz S, Wieland T. A novel player in cellular hypertrophy: Giβγ/PI3K-dependent activation of the RacGEF TIAM-1 is required for α₁-adrenoceptor induced hypertrophy in neonatal rat cardiomyocytes. J Mol Cell Cardiol. 2012 Aug;53(2):165-75.

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