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    CARFI

    CARFI

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    CARFI CARdiovascular Function In vitro

    Presentation

    Pole

    Platform for the investigation of vascular reactivity

    Presentation

    Numerous platforms offer cardiovascular studies with ultrasound analysis, histological or biochemical measurements. Much less offer analysis of vascular functions large artery such as the aorta and none offers functional study of the small resistance arteries. Thus, based on the expertise of BNMI in the analysis of vascular function in resistance arteries we have mounted a plateform for vascular exploration of small arteries: analysis of vascular reactivity in vitro and in vivo with 3 axes.

    •    Vascular functions and structure in small animals (mice and rats):

    •  Analysis of vascular functions and structure in animal models of human diseases 

    •  Use of endothelium-dependent dilatation as a test for the study of antioxidant and antidiabetic substances (actually plants extracts and derivatives).

     

    •  Vascular functions and structure in human small blood vessels:

    •  Analysis of vascular functions (endothelium and smooth muscle) and structure

    •  Inclusion of tissues and data in the local data base (CRB)

     

    • Vascular phenotyping of the whole kidney:

    • Analysis of vascular functions (endothelium and smooth muscle) and structure.

    • Analysis of the effuent (ELISA / cytokines, NOx measurements…etc)

    Responsible(s)

    daniel.henrion @ univ-angers.fr

    Research topics

    Research / expertise topics

    CARFI aims to provide standardized high-quality data on vascular reactivity in vitro.

     

    Technology available:

    • Telemetry for rats and mice (DSI)
    • Tail cuff for rats and mice (DSI)
    • Arterial catheterisation technique for invasing monitoring (blood pressure, Millar)
    • Flowmeter transonic for arterial blood flow measurements  in arteries in vivo (Emka)
    • Pressure myograph (LSI, Burlington, VT)
    • Four-channel wire myograph (Danis Myotech, DK)

     

     

     

     

    Know-how

    Service delivery

    In vivo experiments :

     

    • Tail cuff blood pressure measurement:


    This simple method is realized on vigils animals, slightly constrained. This simple method of reference is to determine the minimum pressure against able to stop arterial blood flow by inflating a cuff around the tail. This non-invasive method for examining animals without an anesthetic effect and repeating experiments many times as necessary during the protocol.

     

     

     

    • Telemetry:


    Telemetry allows measuring parameters such as systolic and diastolic pressure or heart rate on awake, mobile animals in their cages through a lead implanted subcutaneously. This technology allows evaluating several physiological signals without disturbing the animal and over a period of a few days to some months.

     


     

    Flow meter (Transonnic Emka): This is the method of reference forblood flow measurement on anesthetized animal.

     

     

    Ex vivo experiments :

     A group of six pressure-arteriographs and five four-channel wire myographs is dedicated to the in vitro study of endothelial and muscular functions in isolated arteries. This facility is open to all members of the laboratory and to other laboratory in France and abroad. Vascular reactivity is investigated after in vivo measurement of the main cardiovascular parameters (blood pressure using tail cuff or telemetry, local blood flow using Transonic probes). Vascular reactivity is performed on vascular samples (from aorta to resistance arteries 100µm wide).

     

    • Pressure myography:

    • Flow mediated dilation
    • Myogenic tone
    • Remodeling parameters


     

    • Four channel wire myograph :

    Wire Myograph Systems are used to measure force in small rings of muscle tissue. The smallest possible diameter is about 60 microns :


    •  Vascular smooth muscle function
    • Vascular endothelium function
    • Length-tension relationships
    • Wall tension & morphometric measurements
    • Assessment of pharmacological reactivity  and electric stimulation

     

     

     

     

     

    • Organ bath :

    Pressure-flow relationship  and assessment of pharmacology on isolated and perfused Kidney and on isolated and perfused mesenteric bed.


     

     

     

    Partnerships

    Industrial partnerships

    Publications involving CARFI  technology (2010-15):

     

    • INSERM, Nantes : Guilluy C, Bregeon J, Toumaniantz G, Rolli-Derkinderen M, Retailleau K, Loufrani L, Henrion D, Scalbert E, Bril A, Torres RM, Offermanns S, Pacaud P, Loirand G. The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure. Nature Medicine. 2010;16(2):183-90.
    • Berlin, « Charité » Hospital : Buschmann I, Pries A, Styp-Rekowska B, Hillmeister P, Shi Y, Duelsner A, Hoefer I, Gatzke N, Wang H, Lehmann K, Henrion D, Loufrani L, Hlushchuk R, Djonov V, le Noble F. Pulsatile shear and Gja5 (Connexin-40) modulate arterial identity and remodeling events during flow driven arteriogenesis. Development, 2010 ;137:2187-96.
    • Université de Paris VI- INSERM : Nguyen Dinh Cat A, Griol-Charhbili V, Loufrani L, Labat C, Benjamin L, Farman N, Lacolley P, Henrion D, Jaisser F.  The endothelial mineralocorticoid receptor regulates vasoconstrictor tone and blood pressure. FASEB J. 2010;24:2454-63
    • Monash University, Melbourne, Australia: Koïtka A, Cao Z, Koh P, Watson AM, Sourris KC, Loufrani L, Soro-Paavonen A, Walther T, Woollard KJ, Jandeleit-Dahm KA, Cooper ME, Allen TJ. Angiotensin II subtype 2 receptor blockade and deficiency attenuate the development of atherosclerosis in an apolipoprotein E-deficient mouse model of diabetes. Diabetologia. 2010;53:584-92
    • Université de Lübeck : Lund N, Henrion D, Tiede P, Ziche M, Schunkert H, Ito WD. Vimentin expression influences flow dependent VASP phosphorylation and regulates cell migration and proliferation. Biochem Biophys Res Commun. 2010;395:401-6.
    • PINRA, Angers: Duge de Bernonville T, Guyot S, Paulin JP, Gaucher M, Loufrani L, Henrion D, Derbre S, Guilet D, Richomme P, Dat JF, Brisset MN. Dihydrochalcones: Implication in resistance to oxidative stress and bioactivities against advanced glycation end-products and vasoconstriction. Phytochemistry. 2010;71:443-52.
    • INSERM (CRCNA, Nantes-Angers) : Clere N, Corre I, Faure S, Guihot AL, Vessières E, Chalopin M, Morel A, Coqueret O, Hein L, Delneste Y, Paris F, Henrion D. Deficiency or blockade of angiotensin II type 2 receptor delays tumorigenesis by inhibiting malignant cell proliferation and angiogenesis. Int J Cancer, 2010  
    • Cardiologie, EA université d’Angers : Ghaboura N, Tamareille S, Ducluzeau PH, Grimaud L, Loufrani L, Croué A, Tourmen Y, Henrion D, Furber A, Prunier F. Diabetes mellitus abrogates erythropoietin-induced cardioprotection against ischemic-reperfusion injury by alteration of the RISK/GSK-3β signaling. Basic Res Cardiol. 2011 ; 106:147-62.
    • CHU d’Angers : Ghaboura N, Tamareille S, Ducluzeau PH, Grimaud L, Loufrani L, Croué A, Tourmen Y, Henrion D, Furber A, Prunier F. Diabetes mellitus abrogates erythropoietin-induced cardioprotection against ischemic-reperfusion injury by alteration of the RISK/GSK-3β signaling. Basic Res Cardiol. 2011 ; 106:147-62.
    • PARCC INSERM, Paris: Bergaya S, Faure S, Baudrie V, Rio M, Escoubet B, Bonnin P, Henrion D, Loirand G, Achard JM, Jeunemaitre X, and Hadchouel J. WNK1 regulates vasoconstriction and blood pressure response to alpha 1-adrenergic stimulation in mice. Hypertension 58: 439-445, 2011.
    • INSERM, Toulouse: Adlanmerini M, Solinhac R, Abot A, Fabre A, Raymond-Letron I, Guihot AL, Boudou F, Sautier L, Vessieres E, Kim SH, Liere P, Fontaine C, Krust A, Chambon P, Katzenellenbogen JA, Gourdy P, Shaul PW, Henrion D, Arnal JF, and Lenfant F. Mutation of the palmitoylation site of estrogen receptor alpha in vivo reveals tissue-specific roles for membrane versus nuclear actions. Proc Natl Acad Sci U S A 111: E283-E290, 2013
    • College de France, INSERM, Paris : Bouleti C, Mathivet T, Coqueran B, Serfaty JM, Lesage M, Berland E, Ardidie-Robouant C, Kauffenstein G, Henrion D, Lapergue B, Mazighi M, Duyckaerts C, Thurston G, Valenzuela DM, Murphy AJ, Yancopoulos GD, Monnot C, Margaill I, and Germain S. Protective effects of angiopoietin-like 4 on cerebrovascular and functional damages in ischaemic stroke. Eur Heart J 34: 3657-3668, 2013
    • Charité University, Berlin : Cristofaro B, Shi Y, Faria M, Suchting S, Leroyer AS, Trindade A, Duarte A, Zovein AC, Iruela-Arispe ML, Nih LR, Kubis N, Henrion D, Loufrani L, Todiras M, Schleifenbaum J, Gollasch M, Zhuang ZW, Simons M, Eichmann A, and le Noble F. Dll4-Notch signaling determines the formation of native arterial collateral networks and arterial function in mouse ischemia models. Development 140: 1720-1729, 2013.
    • INSERM, Toulouse: Abot A, Fontaine C, Buscato M, Solinhac R, Flouriot G, Fabre A, Drougard A, Rajan S, Laine M, Milon A, Muller I, Henrion D, Adlanmerini M, Valera MC, Gompel A, Gerard C, Pequeux C, Mestdagt M, Raymond-Letron I, Knauf C, Ferriere F, Valet P, Gourdy P, Katzenellenbogen BS, Katzenellenbogen JA, Lenfant F, Greene GL, Foidart JM, and Arnal JF. The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor alpha modulation, uncoupling nuclear and membrane activation. EMBO Mol Med, 2014.
    • INSERM, Toulouse: Adlanmerini M, Solinhac R, Abot A, Fabre A, Raymond-Letron I, Guihot AL, Boudou F, Sautier L, Vessieres E, Kim SH, Liere P, Fontaine C, Krust A, Chambon P, Katzenellenbogen JA, Gourdy P, Shaul PW, Henrion D, Arnal JF, and Lenfant F. Mutation of the palmitoylation site of estrogen receptor alpha in vivo reveals tissue-specific roles for membrane versus nuclear actions. Proc Natl Acad Sci U S A 111: E283-290, 2014.
    • Paris V University: Baron S, Bedarida T, Cottart CH, Vibert F, Vessieres E, Ayer A, Henrion D, Hommeril B, Paul JL, Renault G, Saubamea B, Beaudeux JL, Procaccio V, and Nivet-Antoine V. Dual effects of resveratrol on arterial damage induced by insulin resistance in aged mice. J Gerontol A Biol Sci Med Sci 69: 260-269, 2014.
    • Paris V University: Bedarida T, Baron S, Vessieres E, Vibert F, Ayer A, Marchiol-Fournigault C, Henrion D, Paul JL, Noble F, Golmard JL, Beaudeux JL, Cottart CH, and Nivet-Antoine V. High-protein-low-carbohydrate diet: deleterious metabolic and cardiovascular effects depend on age. Am J Physiol Heart Circ Physiol 307: H649-657, 2014.

     

     

     

    Contacts

    Postal address

    MITOVASC

    UMR CNRS 6015 - INSERM U1083
    Bâtiment IRIS 2
    3 rue Roger Amsler
    49100 ANGERS
    FRANCE
    Phone : +33244688260
    Fax : +33244688261


    Responsible(s)

    daniel.henrion @ univ-angers.fr

    Contacts

    Daniel Henrion : +33244688275
    Emilie Vessières : +33244688267