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Stefan Janssens
Cell and Gene Transfer in Ischaemic Heart Disease and Pulmonary Hypertension
VIB Vesalius Research Center, K.U.Leuven
MD: Univ. of Leuven, Leuven, Belgium, '84
PhD: Univ. of Leuven, Leuven, Belgium, '92
Research Fellow at MGH, Harvard Univ., Boston, USA, '89-'92
VIB Group leader since 1996 |
e-mail
phone +32 16 34 61 82
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Current team members
Group leader: Stefan Janssens
Postdoctoral scientist: Peter Pokreisz
Support personnel: Hilde Gillijns
Keywords
cardiovascular development and disease - gene transfer - hypertension - NO and guanylate cyclase - myocardial infarction
Science
Gene and cell therapy for experimental pulmonary hypertension.
- Both acute and chronic rodent models of pulmonary hypertension have been used to test the efficacy of aerosol gene transfer with genes encoding vasodilatory, antithrombotic and antiproliferative gene products. Different NO-synthase isoforms were overexpressed in the lungs to inhibit hypoxic pulmonary hypertension as well as pulmonary vascular remodeling associated with chronic hypoxia. We will next investigate if gene transfer strategies are able to reverse established pulmonary hypertension (deremodeling studies). Recently, we have also explored the role of cytochrome P450 epoxygenase which mediate production of arachidonic acid metabolites with NO-independent vasomotor effects via hyperpolarization of smooth muscle cells.
- In the years to come the potential of endothelial progenitor cells (EPCs) and of multipotent adult progenitor cells (MAPCs) to home in on hypertensive and remodeled pulmonary vessels to alter the imbalance between vasodilatory and vasoconstrictor mediator release will be investigated. To do so we are characterizing new rodent models of monocrotaline pyrrole–induced pulmonary hypertension.
- Similarly, we will specifically focus on right ventricular function in murine models of pulmonary hypertension as RV dysfunction and development of cor pulmonale is of critical importance in determining the clinical outcome in patients with pulmonary hypertension. In collaboration with the VIB microarray core facilities we have started to analyse differential gene expression patterns in the RV of transgenic mice which have been generated in our group and which may confer benefit in the presence of increased RV afterload. In a first approach we will focus on mice with cardiomyocyte-specific overexpression of constitutitve NO-synthase, which were shown in our lab to be protected against maladaptive remodeling in the volume-overloaded left ventricle. We will correlate these changes with observed hemodynamic alterations (conductance measurements), structural remodeling (matrix remodeling and cardiomyocyte hypertrophy) and molecular adaptations. These studies will provide valuable new insights in the pathophysiology and molecular mechanisms of pulmonary hypertension.
Selected Publications
Janssens S
Stem cells in the treatment of heart disease
ANNU REV MED 61, 287-300, 2010
Pokreisz P, Vandenwijngaert S, Bito V, Van Den Bergh A, Lenaerts I, Busch C, Marsboom G, Gheysens O, Vermeersch P, Biesmans L, Liu X, Gillijns H, Pellens M, Van Lommel A, Buys E, Schoonjans L, Vanhaecke J, Verbeken E, Sipido K, Herijgers P, Bloch K, Janssens S
Ventricular phosphodiesterase-5 expression is increased in patients with advanced heart failure and contributes to adverse ventricular remodeling after myocardial infarction in mice
CIRCULATION 119, 408-16, 2009
Ichinose F, Buys E, Neilan T, Furutani E, Morgan J, Jassal D, Graveline A, Searles R, Lim C, Kaneki M, Picard M, Scherrer-Crosbie M, Janssens S, Liao R, Bloch K
Cardiomyocyte-specific overexpression of nitric oxide synthase 3 prevents myocardial dysfunction in murine models of septic shock
CIRC RES 100, 130-9, 2007
Liu X, Huang Y, Pokreisz P, Vermeersch P, Marsboom G, Swinnen M, Verbeken E, Santos J, Pellens M, Gillijns H, Van De Werf F, Bloch K, Janssens S
Nitric oxide inhalation improves microvascular flow and decreases infarction size after myocardial ischemia and reperfusion
J AM COLL CARDIOL 50, 808-17, 2007
Sinnaeve P, Chiche d, Gillijns H, Van Pelt N, Wirthlin D, Van De Werf F, Collen D, Bloch d, Janssens S
Overexpression of a constitutively active protein kinase G mutant reduces neointima formation and in-stent restenosis
CIRCULATION 105, 2911-2916, 2002
Search Publications
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